title: CRH knockout inhibits the murine innate immune responses in association with endoplasmic reticulum stress after thermal injury.
abstract: BACKGROUND
  Previous studies in our laboratory have demonstrated the hypothalamus destruction and adrenalectomy could blunt the innate immunity while boosting the excessive inflammation after injury. We aimed to investigate the effects of corticotrophin-releasing hormone knockout (CRH KO) on the innate immune responses in macrophages as well as to elucidate the underlying mechanism.
  
  
  METHODS
  The chemotaxis and phagocytosis activities of macrophages, bacteria translocation, plasma tumor necrosis factor (TNF)-α secretion, and intestinal injury were observed in the presence of the endoplasmic reticulum stress after thermal injury in CRH KO mice. Meanwhile, the messenger RNA (mRNA) and protein expression of glucose response protein 78 (GRP78), X-box binding protein 1 (XBP1), and activating transcription factor 6 (ATF6) in macrophages was also determined.
  
  
  RESULTS
  After thermal injury, the chemotaxis and phagocytosis of peritoneal macrophages were increased, which were both reversed by CRH gene deficiency. The gut-derived bacteria translocation to liver tissues, lung tissues and mesenteric lymph nodes was significantly strengthened in CRH KO mice compared with CRH wild-type littermates. Circulating TNF-α level was increased markedly in response to thermal injury and CRH KO further increased its secretion. Furthermore, the mRNA and protein levels of GRP78, XBP1, and ATF6 in peritoneal macrophages increased, while their expressions in CRH KO mice all decreased significantly. CRH KO mice showed enhancement of inflammatory responses and severe tissue injuries after thermal injury.
  
  
  CONCLUSIONS
  CRH exerted immune defensive actions on immune cells and organs in the early phase of injury, suggesting that the underlying mechanisms are related to endoplasmic reticulum stress.
authors: State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Changjiang Zhilu, Daping, Chongqing, P. R. China.
authors: Ce
authors: C
authors: Yang
authors: State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Changjiang Zhilu, Daping, Chongqing, P. R. China.
authors: Wenting
authors: W
authors: Gao
authors: State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Changjiang Zhilu, Daping, Chongqing, P. R. China.
authors: Xuetao
authors: X
authors: Yang
authors: State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Changjiang Zhilu, Daping, Chongqing, P. R. China.
authors: Haiyan
authors: H
authors: Wang
authors: State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Changjiang Zhilu, Daping, Chongqing, P. R. China.
authors: Juan
authors: J
authors: Du
authors: State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Changjiang Zhilu, Daping, Chongqing, P. R. China.
authors: Hejiang
authors: H
authors: Zhong
authors: State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Changjiang Zhilu, Daping, Chongqing, P. R. China.
authors: Linlin
authors: L
authors: Zhou
authors: State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Changjiang Zhilu, Daping, Chongqing, P. R. China.
authors: Jianyun
authors: J
authors: Zhou
authors: Department of Neurosurgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Changjiang Zhilu, Daping, Chongqing, P. R. China.
authors: Yundong
authors: Y
authors: Zhang
authors: State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Changjiang Zhilu, Daping, Chongqing, P. R. China. Electronic address: hellojjx@126.com.
authors: Jianxin
authors: J
authors: Jiang
mesh_terms: D000818:Animals; D002056:Burns / Q000276:immunology*; D002633:Chemotaxis / Q000276:immunology; D003346:Corticotropin-Releasing Hormone / Q000235:genetics* / Q000276:immunology; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000276:immunology*; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology*; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010537:Peritoneum / Q000166:cytology
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717248:Hspa5 protein, mouse; D003346:Corticotropin-Releasing Hormone