title: Psychological stress promotes neutrophil infiltration in colon tissue through adrenergic signaling in DSS-induced colitis model.
abstract: Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory condition. Psychological stress has been postulated to affect the clinical symptoms and recurrence of IBD. The exact molecular mechanisms are not fully understood. In the present study, we demonstrate that psychological stress promotes neutrophil infiltration into colon tissues in dextran sulfate sodium (DSS)-induced colitis model. The psychological stress resulted in abnormal expression of the proinflammatory cytokines (IL-1β, IL-6, IL-17A, and IL-22) and neutrophil chemokines (CXCL1 and CXCL2) and overactivation of the STAT3 inflammatory signaling pathway. Under chronic unpredictable stress, the adrenergic nervous system was markedly activated, as the expression of tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, in bone marrow and colonic epithelium was enhanced, especially in the myenteric ganglia. The β-AR agonist isoproterenol mimicked the effects of psychological stress on neutrophilia, neutrophil infiltration, and colonic damage in DSS-induced colitis. The β1-AR/β2-AR inhibitor propranolol reduced the numbers of the neutrophils in the circulation, suppressed neutrophil infiltration into colonic tissues, and attenuated the colonic tissue damage promoted by chronic stress. Propranolol also abolished stress-induced upregulation of proinflammatory cytokines and neutrophil chemokines. Our data reveal a close linkage between the β1-AR/β2-AR activation and neutrophil trafficking and also suggest the critical roles of adrenergic nervous system in exacerbation of inflammation and damage of colonic tissues in experimental colitis. The current study provides a new insight into the mechanisms underlying the association of psychological stress with excessive inflammatory response and pathophysiological consequences in IBD. The findings also suggest a potential application of neuroprotective agents to prevent relapsing immune activation in the treatment of IBD.
authors.affiliation: Institute of Basic Medical Sciences, Beijing 100850, PR China.
authors.forename: Que
authors.initials: Q
authors.lastname: Deng
authors.affiliation: Institute of Basic Medical Sciences, Beijing 100850, PR China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Chen
authors.affiliation: Laboratory of Cellular and Molecular Immunology, Medical School of Henan University, Kaifeng 475004, PR China.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China.
authors.forename: Fengjun
authors.initials: F
authors.lastname: Xiao
authors.affiliation: Institute of Basic Medical Sciences, Beijing 100850, PR China.
authors.forename: Liang
authors.initials: L
authors.lastname: Guo
authors.affiliation: Institute of Basic Medical Sciences, Beijing 100850, PR China.
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.affiliation: Institute of Basic Medical Sciences, Beijing 100850, PR China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Institute of Basic Medical Sciences, Beijing 100850, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Institute of Basic Medical Sciences, Beijing 100850, PR China.
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Wang
authors.affiliation: Laboratory of Cellular and Molecular Immunology, Medical School of Henan University, Kaifeng 475004, PR China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Xie
authors.affiliation: Department of Urology, The First Affiliated Hospital, General Hospital of PLA, Beijing 100048, PR China.
authors.forename: Siyong
authors.initials: S
authors.lastname: Qi
authors.affiliation: Department of Urology, The First Affiliated Hospital, General Hospital of PLA, Beijing 100048, PR China.
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Yin
authors.affiliation: Department of Urology, The First Affiliated Hospital, General Hospital of PLA, Beijing 100048, PR China.
authors.forename: Jiangping
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Cancer Biotherapy, Cancer Institute, Tangshan People's Hospital, Tangshan 063001, PR China.
authors.forename: Xintian
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Cancer Biotherapy, Cancer Institute, Tangshan People's Hospital, Tangshan 063001, PR China.
authors.forename: Jiangong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Institute of Basic Medical Sciences, Beijing 100850, PR China. Electronic address: ning_guo@sina.com.
authors.forename: Ning
authors.initials: N
authors.lastname: Guo
authors.affiliation: Laboratory of Cellular and Molecular Immunology, Medical School of Henan University, Kaifeng 475004, PR China. Electronic address: mayf@henu.edu.cn.
authors.forename: Yuanfang
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Institute of Basic Medical Sciences, Beijing 100850, PR China. Electronic address: sm200@sohu.com.
authors.forename: Ming
authors.initials: M
authors.lastname: Shi
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D018925:Chemokines / Q000097:blood*; D003092:Colitis / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy; D004195:Disease Models, Animal; D007249:Inflammation / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy; D007378:Interleukins / Q000097:blood*; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration / Q000276:immunology*; D011433:Propranolol / Q000008:administration & dosage / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013315:Stress, Psychological / Q000097:blood / Q000150:complications / Q000188:drug therapy
chemical_list: D000319:Adrenergic beta-Antagonists; D018925:Chemokines; D007378:Interleukins; D011943:Receptors, Adrenergic, beta; D011433:Propranolol
keywords: Catecholamine; Inflammatory bowel disease; Neutrophil; β-AR