IMMUNOLOGICAL ASPECTS OF HEMORRHAGE

Summary

Principal Investigator: Irshad H Chaudry
Abstract: DESCRIPTION (provided by applicant): Our studies demonstrate marked immune depression, i.e., decreased T cell and macrophage (MO) antigen presentation function and increased lethality from subsequent sepsis, in young males;but not in proestrus females following trauma-hemorrhage (T-H). The results also demonstrate a compartmentalized response in males;splenic and peritoneal MO (SMO, PMO) cytokine release is decreased, while Kupffer cells (KC) and alveolar MO cytokine release is markedly increased. Thus, it is important to identify agents that have global immunomodulating effects under those conditions. Our findings that 17p-estradiol (E2) has the unique ability to protect immune cell responses following T-H, and that flutamide [androgen receptor (AR) antagonist] also utilizes E2-mediated pathway in restoring immune functions in males, leads us to hypothesize that female sex steroids play a critical role in maintaining cell signaling homeostasis and the immune cell functions in various tissue compartments after T-H. Since activation of MO/T cell precedes a cascade of signaling events, we will characterize signaling alterations in Kupffer cells, alveolar MO, PMO, SMO, splenic dendritic cells (DC) and splenic T cells, peripheral blood monocytes and T cells and correlate those changes with their effector responses (MO and DC: MO/DC antigen presentation and ability to release cytokines;T cells: ability to differentiate into Th1/Th2 phenotype following T-H in males/proestrus females). Estrogen receptor (ER) and AR expression will also be evaluated. Studies will also examine if modulating alterations in one or more signaling pathways, identified in the above studies, by treating mice with E2 or flutamide following T-H normalizes MO, DC and T cell effector responses. Furthermore, we will use E2 (cell permeable) and E2 conjugated with BSA (bovine serum albumin;cell impermeable) to determine the contribution of nuclear vs. surface receptor in restoring immune cell responses after T-H. Additional studies will examine whether E2 and flutamide utilize a common or different signaling pathway in mediating their salutary effects after T-H. Moreover, ER-a and ER-(3 knockout (KO) mice will be used to determine the relative role of ER-a and ER-p in normalizing immune cell responses after T-H. Studies will also utilize other available KOs and pharmacological agents to delineate which of the signaling pathway(s) is/are critical to E2-mediated salutary effects in various tissue compartments following T-H. Finally, we will determine whether the agent(s) that normalizes immune cell responses has/have any salutary effects in decreasing the mortality rates from sepsis following T-H. The proposed studies using state-of-the-art cellular/molecular techniques should provide innovative information identifying the mechanism(s) by which sex steroids maintain or deteriorate immune cell functions in various tissue compartments following T-H, and also for developing gender specific therapy for preventing immune depression and reducing mortality from sepsis in trauma victims.
Funding Period: ----------------1988 - ---------------2011-
more information: NIH RePORT

Top Publications

  1. ncbi The effects of estrogen on various organs: therapeutic approach for sepsis, trauma, and reperfusion injury. Part 2: liver, intestine, spleen, and kidney
    Takashi Kawasaki
    Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294, USA
    J Anesth 26:892-9. 2012
  2. ncbi 17beta-Estradiol: a novel hormone for improving immune and cardiovascular responses following trauma-hemorrhage
    Mashkoor A Choudhry
    Center for Surgical Research and Department of Surgery, The University of Alabama at Birmingham, 1670 University Blvd, Birmingham, AL 35294 0019, USA
    J Leukoc Biol 83:518-22. 2008
  3. ncbi Metabolic modulators following trauma sepsis: sex hormones
    Ya Ching Hsieh
    Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294 0019, USA
    Crit Care Med 35:S621-9. 2007
  4. pmc 17beta-Estradiol's salutary effects on splenic dendritic cell functions following trauma-hemorrhage are mediated via estrogen receptor-alpha
    Takashi Kawasaki
    Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294, United States
    Mol Immunol 45:376-85. 2008
  5. ncbi Estrogen receptor-alpha predominantly mediates the salutary effects of 17beta-estradiol on splenic macrophages following trauma-hemorrhage
    Takao Suzuki
    Center for Surgical Research and Dept of Surgery, Univ of Alabama, at Birmingham, 1670 Univ Blvd, Volker Hall, Rm G094, Birmingham, AL 35294 0019, USA
    Am J Physiol Cell Physiol 293:C978-84. 2007
  6. pmc 17 Beta-estradiol normalizes Toll receptor 4, mitogen activated protein kinases and inflammatory response in epidermal keratinocytes following trauma-hemorrhage
    Fariba Moeinpour
    Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294 0019, USA
    Mol Immunol 44:3317-23. 2007
  7. ncbi Salutary effects of 17beta-estradiol on T-cell signaling and cytokine production after trauma-hemorrhage are mediated primarily via estrogen receptor-alpha
    Takao Suzuki
    Center for Surgical Research and Dept of Surgery, University of Alabama at Birmingham, AL 35294 0019, USA
    Am J Physiol Cell Physiol 292:C2103-11. 2007
  8. ncbi Downregulation of migration inhibitory factor is critical for estrogen-mediated attenuation of lung tissue damage following trauma-hemorrhage
    Ya Ching Hsieh
    Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama 35294 0019, USA
    Am J Physiol Lung Cell Mol Physiol 292:L1227-32. 2007
  9. ncbi TLR4 regulates Kupffer cell chemokine production, systemic inflammation and lung neutrophil infiltration following trauma-hemorrhage
    Michael Frink
    Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, 1670 University Boulevard, Birmingham, AL 35294, USA
    Mol Immunol 44:2625-30. 2007
  10. ncbi Mechanism of salutary effects of finasteride on post-traumatic immune/inflammatory response: upregulation of estradiol synthesis
    Michael Frink
    Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama 35294 0019, USA
    Ann Surg 246:836-43. 2007

Scientific Experts

  • Martin Schwacha
  • Irshad H Chaudry
  • Mashkoor A Choudhry
  • Kirby I Bland
  • Takashi Kawasaki
  • Ya Ching Hsieh
  • Michael Frink
  • Takao Suzuki
  • Chi Hsun Hsieh
  • Bjoern M Thobe
  • William J Hubbard
  • Frank Hildebrand
  • Raghavan Raju
  • Huang Ping Yu
  • Martin K Angele
  • Christian P Schneider
  • Takeshi Matsutani
  • Tomoharu Shimizu
  • Hans Christoph Pape
  • Eike A Nickel
  • Jun Te Hsu
  • Fariba Moeinpour
  • Ailing Lu
  • Shih Ching Kang
  • Bixi Jian
  • Satoshi Fujimi
  • Masao Miyashita
  • Koji Sasajima
  • James A Lederer
  • Loring W Rue
  • Steven L Kunkel
  • Björn M Thobe
  • Rui Zheng
  • Sebastian Pratschke
  • Chika Kawasaki
  • Takeyoshi Sata
  • Joachim Voss
  • Irshad Chaudry
  • Deli Wang
  • Dongquan Chen
  • Jianguo G Chen
  • Jianguo Chen
  • Mohammad Athar
  • Wen Hong Kan
  • Luiz F Poli de Figueiredo
  • Laura Timares
  • Shunhua Hu
  • George Pan
  • Laszlo Szalay
  • T S Anantha Samy

Detail Information

Publications56

  1. ncbi The effects of estrogen on various organs: therapeutic approach for sepsis, trauma, and reperfusion injury. Part 2: liver, intestine, spleen, and kidney
    Takashi Kawasaki
    Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294, USA
    J Anesth 26:892-9. 2012
    ..The findings gained from the experimental studies will help in designing innovative therapeutic approaches for the treatment of sepsis, trauma, and reperfusion injury patients...
  2. ncbi 17beta-Estradiol: a novel hormone for improving immune and cardiovascular responses following trauma-hemorrhage
    Mashkoor A Choudhry
    Center for Surgical Research and Department of Surgery, The University of Alabama at Birmingham, 1670 University Blvd, Birmingham, AL 35294 0019, USA
    J Leukoc Biol 83:518-22. 2008
    ....
  3. ncbi Metabolic modulators following trauma sepsis: sex hormones
    Ya Ching Hsieh
    Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294 0019, USA
    Crit Care Med 35:S621-9. 2007
    ..Additionally, sex steroids regulate inflammatory cytokines that cause hypermetabolism/catabolism via acute phase response, leading to increased morbidity and mortality...
  4. pmc 17beta-Estradiol's salutary effects on splenic dendritic cell functions following trauma-hemorrhage are mediated via estrogen receptor-alpha
    Takashi Kawasaki
    Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294, United States
    Mol Immunol 45:376-85. 2008
    ..Since PPT administration following trauma-hemorrhage was more effective in normalizing splenic DC functions than DPN, the salutary effects of 17beta-estradiol on splenic DC functions are mediated predominantly via ER-alpha...
  5. ncbi Estrogen receptor-alpha predominantly mediates the salutary effects of 17beta-estradiol on splenic macrophages following trauma-hemorrhage
    Takao Suzuki
    Center for Surgical Research and Dept of Surgery, Univ of Alabama, at Birmingham, 1670 Univ Blvd, Volker Hall, Rm G094, Birmingham, AL 35294 0019, USA
    Am J Physiol Cell Physiol 293:C978-84. 2007
    ....
  6. pmc 17 Beta-estradiol normalizes Toll receptor 4, mitogen activated protein kinases and inflammatory response in epidermal keratinocytes following trauma-hemorrhage
    Fariba Moeinpour
    Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294 0019, USA
    Mol Immunol 44:3317-23. 2007
    ..These findings suggest that 17beta-estradiol normalizes epidermal keratinocytes inflammatory responses following trauma-hemorrhage by preventing the upregulation of TLR4-mediated MAPK activation...
  7. ncbi Salutary effects of 17beta-estradiol on T-cell signaling and cytokine production after trauma-hemorrhage are mediated primarily via estrogen receptor-alpha
    Takao Suzuki
    Center for Surgical Research and Dept of Surgery, University of Alabama at Birmingham, AL 35294 0019, USA
    Am J Physiol Cell Physiol 292:C2103-11. 2007
    ....
  8. ncbi Downregulation of migration inhibitory factor is critical for estrogen-mediated attenuation of lung tissue damage following trauma-hemorrhage
    Ya Ching Hsieh
    Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama 35294 0019, USA
    Am J Physiol Lung Cell Mol Physiol 292:L1227-32. 2007
    ..These results suggest that the protective effects of E(2) on lung injury following trauma-hemorrhage are mediated via downregulation of lung MIF and TLR4-induced cytokine/chemokine production...
  9. ncbi TLR4 regulates Kupffer cell chemokine production, systemic inflammation and lung neutrophil infiltration following trauma-hemorrhage
    Michael Frink
    Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, 1670 University Boulevard, Birmingham, AL 35294, USA
    Mol Immunol 44:2625-30. 2007
    ..These findings suggest that functional TLR4 signaling is critical in mediating the inflammatory response following trauma hemorrhage. Thus, modulation of the TLR4 after injury may serve as a future therapeutic target in trauma patients...
  10. ncbi Mechanism of salutary effects of finasteride on post-traumatic immune/inflammatory response: upregulation of estradiol synthesis
    Michael Frink
    Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama 35294 0019, USA
    Ann Surg 246:836-43. 2007
    ..The aim of this study was to evaluate whether pretreatment with finasteride, a 5alpha-reductase inhibitor, improves immune functions after trauma-hemorrhage...
  11. pmc Trauma and immune response--effect of gender differences
    Mashkoor A Choudhry
    Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294, USA
    Injury 38:1382-91. 2007
    ..Since these cells are also the cells that produce cytokines, local synthesis of active steroids in these cells may become the significant factor in modulating their cytokine production...
  12. ncbi Trauma-hemorrhage inhibits splenic dendritic cell proinflammatory cytokine production via a mitogen-activated protein kinase process
    Takashi Kawasaki
    Center for Surgical Research, Univ of Alabama at Birmingham, 1670 Univ Blvd, Volker Hall, Rm G094, Birmingham, AL 35294 0019, USA
    Am J Physiol Cell Physiol 294:C754-64. 2008
    ..Hyporesponsiveness of splenic DCs was also found after stimulation with the TLR2 agonist zymosan. Our results may thus explain the profound immunosuppression that is known to occur under those conditions...
  13. ncbi The effects of estrogen on various organs: therapeutic approach for sepsis, trauma, and reperfusion injury. Part 1: central nervous system, lung, and heart
    Takashi Kawasaki
    Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294, USA
    J Anesth 26:883-91. 2012
    ..This article reviews studies delineating the mechanism by which estrogen regulates cerebral nervous, lung, and heart systems in an experimental model of sepsis, trauma, or reperfusion injury...
  14. pmc Gender differences in sepsis: cardiovascular and immunological aspects
    Martin K Angele
    Department of Surgery Klinikum Grosshadern Munich, Germany
    Virulence 5:12-9. 2014
    ..Prospective patient studies are required for transferring those important experimental findings into the clinical arena. ..
  15. pmc Estradiol's salutary effects on keratinocytes following trauma-hemorrhage are mediated by estrogen receptor (ER)-alpha and ER-beta
    Fariba Moeinpour
    Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama 35294 0019, USA
    Mol Med 14:689-96. 2008
    ..PPT and DPN administration were equally effective in normalizing the inflammatory response of keratinocytes, indicating that both ER-alpha and ER-beta mediate the salutary effects of estrogen on keratinocytes after trauma-hemorrhage...
  16. ncbi The role of MIP-1 alpha in the development of systemic inflammatory response and organ injury following trauma hemorrhage
    Chi Hsun Hsieh
    Center for Surgical Research and Department of Surgery, University of Alabama, Birmingham, AL 35294, USA
    J Immunol 181:2806-12. 2008
    ..Thus, interventions that reduce MIP-1alpha levels following T-H should be useful in decreasing the deleterious inflammatory consequence of trauma...
  17. pmc Bench-to-bedside review: latest results in hemorrhagic shock
    Martin K Angele
    Department of Surgery, Klinikum Grosshadern, Ludwig Maximilians University, Marchionistrasse 15, 81377 Munich, Germany
    Crit Care 12:218. 2008
    ..Further randomized controlled multicenter clinical trials are needed that utilize standardized criteria for enrolling patients, but existing ethical requirements must be maintained...
  18. ncbi Sex steroids/receptor antagonist: their use as adjuncts after trauma-hemorrhage for improving immune/cardiovascular responses and for decreasing mortality from subsequent sepsis
    Raghavan Raju
    Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama 35294 0019, USA
    Anesth Analg 107:159-66. 2008
    ....
  19. pmc Burn injury-induced alterations in wound inflammation and healing are associated with suppressed hypoxia inducible factor-1alpha expression
    Martin G Schwacha
    Department of Surgery, Division of Trauma and Emergency Surgery, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229 3900, USA
    Mol Med 14:628-33. 2008
    ..In conclusion, these findings suggest that HIF-1alpha and the inflammatory response play a significant role in wound healing, and reduced levels of HIF-1alpha contribute to the impaired healing response post-burn...
  20. pmc Estrogen: a novel therapeutic adjunct for the treatment of trauma-hemorrhage-induced immunological alterations
    Raghavan Raju
    Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama 35294 0019, USA
    Mol Med 14:213-21. 2008
    ..The results of the studies exemplify the promise of estrogen as a therapeutic adjunct in treating adverse pathophysiological conditions following trauma-hemorrhage...
  21. ncbi Downregulation of TLR4-dependent ATP production is critical for estrogen-mediated immunoprotection in Kupffer cells following trauma-hemorrhage
    Ya Ching Hsieh
    Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama, USA
    J Cell Physiol 211:364-70. 2007
    ..Taken together, these findings suggest that downregulation of TLR4-dependent ATP production is critical to 17beta-estradiol-mediated immunoprotection in Kupffer cells following trauma-hemorrhage...
  22. ncbi Effects of 17beta-estradiol and flutamide on splenic macrophages and splenocytes after trauma-hemorrhage
    Frank Hildebrand
    Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, G094 Volker Hall, 1670 University Boulevard, Birmingham, AL 35294 0019, USA
    Cytokine 36:107-14. 2006
    ..However, flutamide administration in combination with estrogen does not provide any significant, additional effects over 17beta-estradiol administration alone...
  23. ncbi Young and middle-age associated differences in cytokeratin expression after bone fracture, tissue trauma, and hemorrhage
    Takeshi Matsutani
    Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, G 094 Volker Hall, 1670 University Blvd, Birmingham, AL 35294 0019, USA
    Am J Surg 193:61-8. 2007
    ..This study examined whether there is any difference in the lung cytokine and cytokeratin 19 levels between young and middle-aged mice after bone fracture and soft-tissue trauma hemorrhage (Fx-TH)...
  24. ncbi 17 beta-estradiol administration following trauma-hemorrhage prevents the increase in Kupffer cell cytokine production and MAPK activation predominately via estrogen receptor-alpha
    Takao Suzuki
    Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294 0019, USA
    Surgery 140:141-8. 2006
    ..We hypothesized that E2 mediates its salutary effects via ER-alpha and normalization of MAPK under those conditions...
  25. ncbi Effects of 17beta-estradiol and flutamide on inflammatory response and distant organ damage following trauma-hemorrhage in metestrus females
    Frank Hildebrand
    Department of Surgery, University of Alabama at Birmingham, AL 35294 0019, USA
    J Leukoc Biol 80:759-65. 2006
    ....
  26. ncbi Lidocaine depresses splenocyte immune functions following trauma-hemorrhage in mice
    Takashi Kawasaki
    Center for Surgical Research, Department of Surgery, University of Alabama at Birmingham, AL 35294 0019, USA
    Am J Physiol Cell Physiol 291:C1049-55. 2006
    ..The enhanced immunosuppressive effects of lidocaine could contribute to the host's enhanced susceptibility to infection following T-H...
  27. ncbi Gender and susceptibility to sepsis following trauma
    Mashkoor A Choudhry
    Center for Surgical Research, The University of Alabama at Birmingham, Volker Hall, G094, 1670 University Blvd, Birmingham, AL 35294 0019, USA
    Endocr Metab Immune Disord Drug Targets 6:127-35. 2006
    ..The findings obtained from these studies will help in designing innovative therapeutic approaches for the treatment of trauma patients...
  28. ncbi Androstenediol ameliorates alterations in immune cells cytokine production capacity in a two-hit model of trauma-hemorrhage and sepsis
    Takao Suzuki
    Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294, USA
    Cytokine 34:76-84. 2006
    ....
  29. ncbi Src family kinases regulate p38 MAPK-mediated IL-6 production in Kupffer cells following hypoxia
    Björn M Thobe
    Center for Surgical Research, The University of Alabama at Birmingham, Volker Hall G094, 1670 University Boulevard, Birmingham, AL 35294 0019, USA
    Am J Physiol Cell Physiol 291:C476-82. 2006
    ..Thus hypoxia increases KC IL-6 production by p38 MAPK activation via Src-dependent pathway. Src kinases may therefore be a novel therapeutic target for preventing immune dysfunction following low-flow conditions in trauma patients...
  30. ncbi Are the protective effects of 17beta-estradiol on splenic macrophages and splenocytes after trauma-hemorrhage mediated via estrogen-receptor (ER)-alpha or ER-beta?
    Frank Hildebrand
    Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294 0019, USA
    J Leukoc Biol 79:1173-80. 2006
    ..These findings collectively suggest that both receptors appear to play a significant role in mediating the immunoprotective effects of E2 in different tissue compartments following trauma-hemorrhage...
  31. ncbi Influence of gender and age on T-cell responses in a murine model of trauma-hemorrhage: differences between circulating and tissue-fixed cells
    Christian P Schneider
    Center for Surgical Research, Department of Surgery, Univ of Alabama at Birmingham, G 094Volker Hall, 1670 Univ Blvd, Birmingham, AL 35294 0019, USA
    J Appl Physiol 100:826-33. 2006
    ..Age is also an important factor in the immune responses after TH. In view of this, both gender and age should be taken into consideration in evaluating the immune status and in treatment of TH shock...
  32. ncbi Alcohol intoxication and post-burn complications
    Mashkoor A Choudhry
    Center for Surgical Research, Department of Surgery, University of Alabama, Birmingham, AL 35294, USA
    Front Biosci 11:998-1005. 2006
    ..Therefore blood EtOH should be monitored in burn/trauma patients at the time of admission in the emergency room...
  33. pmc Kupffer cells and their mediators: the culprits in producing distant organ damage after trauma-hemorrhage
    Frank Hildebrand
    Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Volker Hall G094, 1670 University Blvd, Birmingham, AL 35294 0019, USA
    Am J Pathol 169:784-94. 2006
    ..These findings suggest that Kupffer cell-derived MCP-1 plays a major role in remote organ dysfunction after trauma-hemorrhage...
  34. pmc MyD88 and Src are differentially regulated in Kupffer cells of males and proestrus females following hypoxia
    Rui Zheng
    Center for Surgical Research, Department of Surgery, University of Alabama at Birmingham, AL 35294 0019, USA
    Mol Med 12:65-73. 2006
    ..Administration of Src inhibitor in hypoxic males prevented increased IL-6 production. Thus, differential regulation of MyD88 and Src in males and females plays an important role in sex-specific immune response following hypoxia...
  35. ncbi The role of MAPK in Kupffer cell toll-like receptor (TLR) 2-, TLR4-, and TLR9-mediated signaling following trauma-hemorrhage
    Bjoern M Thobe
    Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama 35294 0019, USA
    J Cell Physiol 210:667-75. 2007
    ..Thus, Kupffer cell TLR signaling employs different MAPK pathways in eliciting cytokine and chemokine responses following trauma-hemorrhage...
  36. ncbi Monocyte chemoattractant protein-1 influences trauma-hemorrhage-induced distal organ damage via regulation of keratinocyte-derived chemokine production
    Michael Frink
    Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Volker Hall Suite G094, 1670 University Blvd, Birmingham, AL 35294 0019, USA
    Am J Physiol Regul Integr Comp Physiol 292:R1110-6. 2007
    ..These results lead us to conclude that increased levels of MCP-1 cause neutrophil accumulation and distant organ damage by regulating KC production during the postinjury inflammatory response...
  37. ncbi 17beta-Estradiol inhibits keratinocyte-derived chemokine production following trauma-hemorrhage
    Michael Frink
    Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294 0019, USA
    Am J Physiol Lung Cell Mol Physiol 292:L585-91. 2007
    ..These results suggest that E2 prevents lung neutrophil infiltration and organ damage in part by decreasing KC during posttraumatic immune response...
  38. ncbi Impact of sex and age on bone marrow immune responses in a murine model of trauma-hemorrhage
    Christian P Schneider
    Center for Surgical Research, Univ of Alabama at Birmingham, G094Volker Hall, 1670 Univ Blvd, Birmingham, AL 35294 0019, USA
    J Appl Physiol (1985) 102:113-21. 2007
    ....
  39. pmc 17Beta-estradiol downregulates Kupffer cell TLR4-dependent p38 MAPK pathway and normalizes inflammatory cytokine production following trauma-hemorrhage
    Ya Ching Hsieh
    Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294, USA
    Mol Immunol 44:2165-72. 2007
    ....
  40. ncbi Tissue compartment-specific role of estrogen receptor subtypes in immune cell cytokine production following trauma-hemorrhage
    Takao Suzuki
    Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, 1670 Univ Blvd, Volker Hall, Rm G094, Birmingham, AL 35294 0019, USA
    J Appl Physiol 102:163-8. 2007
    ..Both agonists were equally effective on SMPhi and AMPhi. Thus ER subtypes have tissue compartment-specific roles in mediating the effects of 17beta-estradiol on immune cell functions following trauma-hemorrhage...
  41. ncbi Mitochondria play an important role in 17beta-estradiol attenuation of H(2)O(2)-induced rat endothelial cell apoptosis
    Ailing Lu
    Center for Surgical Research, The University of Alabama at Birmingham, Birmingham, Alabama, USA
    Am J Physiol Endocrinol Metab 292:E585-93. 2007
    ..These findings suggest that 17beta-estradiol attenuated H(2)O(2)-induced apoptosis via ER-dependent activation of caspase-9 and -3 in rat endothelial cells through mitochondria...
  42. ncbi Trauma-hemorrhage induces depressed splenic dendritic cell functions in mice
    Takashi Kawasaki
    Center for Surgical Research and Department of Surgery, University of Alabama, 1670 University Boulevard, Birmingham, AL 35294, USA
    J Immunol 177:4514-20. 2006
    ..This depression in Ag presentation could contribute to the host's enhanced susceptibility to sepsis following T-H...
  43. ncbi Liver cytokine production and ICAM-1 expression following bone fracture, tissue trauma, and hemorrhage in middle-aged mice
    Takeshi Matsutani
    Center for Surgical Research, University of Alabama, G 094 Volker Hall, 1670 Univ Blvd, Birmingham, AL 35294 0019, USA
    Am J Physiol Gastrointest Liver Physiol 292:G268-74. 2007
    ..These results collectively suggest that the extent of hepatic damage following Fx-TH is dependent on the age of the subject...
  44. ncbi Role of PPARγ in the salutary effects of 17β-estradiol on Kupffer cell cytokine production following trauma-hemorrhage
    Takao Suzuki
    Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama 35294 0019, USA
    J Cell Physiol 226:205-11. 2011
    ....
  45. pmc Lidocaine suppresses mouse Peyer's Patch T cell functions and induces bacterial translocation
    Takashi Kawasaki
    Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294, USA
    Surgery 149:106-13. 2011
    ..Although local anesthetics are widely used in clinical practice, it remains unclear whether local anesthetics such as lidocaine affect PP T cell functions...
  46. pmc Salutary effects of 17beta-estradiol on Peyer's patch T cell functions following trauma-hemorrhage
    Takashi Kawasaki
    Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, G094 Volker Hall, 1670 University Boulevard, Birmingham, AL 35294, USA
    Cytokine 51:166-72. 2010
    ..E2, PPT or DPN administration normalized these parameters. Since PPT or DPN administration following T-H was effective in normalizing PP T cell functions, the salutary effects of E2 are mediated via ER-alpha and ER-beta...
  47. pmc Hypoxia-induced alteration of mitochondrial genes in cardiomyocytes: role of Bnip3 and Pdk1
    Bixi Jian
    Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama, USA
    Shock 34:169-75. 2010
    ..This study identifies the participation of two important pathways, cell death and glycolytic, and two key proteins, Bnip3 and Pdk1, playing critical roles in these pathways in cardiomyocytes after severe hypoxia...
  48. pmc Trauma-hemorrhage and hypoxia differentially influence kupffer cell phagocytic capacity: role of hypoxia-inducible-factor-1alpha and phosphoinositide 3-kinase/Akt activation
    Chi Hsun Hsieh
    Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294 0019, USA
    Ann Surg 250:995-1001. 2009
    ..We hypothesized that the differences might result from a differential activation of hypoxia-inducible factor (HIF)-1alpha and phosphoinositide 3-kinase (PI3K)/Akt pathway under those conditions...
  49. pmc Suppression of activation and costimulatory signaling in splenic CD4+ T cells after trauma-hemorrhage reduces T-cell function: a mechanism of post-traumatic immune suppression
    Chi Hsun Hsieh
    Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294 0019, USA
    Am J Pathol 175:1504-14. 2009
    ..Dysregulation of the T-cell costimulatory pathway is therefore likely to be a significant contributor to post-traumatic immune suppression...
  50. pmc Impact of thermal injury on wound infiltration and the dermal inflammatory response
    Martin G Schwacha
    Department of Surgery, Division of Trauma and Emergency Surgery, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229 3900, USA
    J Surg Res 158:112-20. 2010
    ....
  51. pmc Mechanism of the salutary effects of estrogen on kupffer cell phagocytic capacity following trauma-hemorrhage: pivotal role of Akt activation
    Chi Hsun Hsieh
    Center for Surgical Research and Department of Surgery, University of Alabama, Birmingham, 35294, USA
    J Immunol 182:4406-14. 2009
    ..Thus, activation of Akt plays a crucial role in mediating the salutary effect of estrogen in restoring trauma-hemorrhage-induced suppression of Kupffer cell phagocytosis...
  52. pmc When apoptosis meets autophagy: deciding cell fate after trauma and sepsis
    Ya Ching Hsieh
    Department of Medical Research, E Da Hospital, I Shou University, Kaohsiung, Taiwan, ROC
    Trends Mol Med 15:129-38. 2009
    ..The inter-relationship between autophagy and apoptosis might unveil novel therapeutic approaches for the detection and treatment of trauma-hemorrhage and sepsis...
  53. pmc Effect of interleukin-15 on depressed splenic dendritic cell functions following trauma-hemorrhage
    Takashi Kawasaki
    Center for Surgical Research, University of Alabama at Birmingham, 1670 University Blvd, Volker Hall, Rm G094, Birmingham, AL 35294 0019, USA
    Am J Physiol Cell Physiol 296:C124-30. 2009
    ..The depression in IL-15 production by splenic DCs could contribute to the host's enhanced susceptibility to infections following T-H...
  54. pmc The role of estrogen and receptor agonists in maintaining organ function after trauma-hemorrhage
    Huang Ping Yu
    Department of Anesthesiology, Chang Gung Memorial Hospital, Taiwan
    Shock 31:227-37. 2009
    ..Thus, alteration or modulation of the prevailing hormone milieu at the time of injury seems to be a novel therapeutic option for improving outcome after injury..
  55. pmc Estrogen suppresses cardiac IL-6 after trauma-hemorrhage via a hypoxia-inducible factor 1 alpha-mediated pathway
    Eike A Nickel
    Department of Surgery, Center for Surgical Research, University of Alabama at Birmingham, Birmingham, Alabama 35294 0019, USA
    Shock 31:354-8. 2009
    ..These results indicate that the beneficial effects of estrogen on cardiac function after trauma-hemorrhage seem to be mediated by the inhibition of HIF-1 alpha expression and activity...