title: Regulation of IL-8 production by complement-activated product, C5a, in vitro and in vivo during sepsis.
abstract: Excessive complement-activated product complement 5a (C5a) has been implicated in the pathogenesis of sepsis development. Herein, we employed in vitro and in vivo models of sepsis to investigate the functional relationship between overtly produced C5a and IL-8. Our data revealed that C5a could strongly amplify IL-8 expression from human whole blood cells induced by LPS and other types of TLR agonists. ERK1/2 and p38, but not JNK, were mainly participated in signaling pathways for IL-8 production. In the whole blood stimulated by Escherichiacoli, C5a levels were quickly elevated and blockage of C5a significantly decreased E. coli-elicited IL-8 production. In the mouse model of sepsis induced by cecal ligation and puncture (CLP), the markedly increased keratinocyte-derived cytokine (KC) could be strongly suppressed by blockage of C5a. These data suggest that excessive C5a functions as a critical inflammatory mediator to enhance IL-8 production mainly through MAPK signaling pathways.
authors.affiliation: Department of Molecular Immunology, Institute of Basic Medical Sciences, Taiping Road, No. 27, Beijing 100850, People's Republic of China.
authors.forename: Liyan
authors.initials: L
authors.lastname: Wang
authors.forename: Gencheng
authors.initials: G
authors.lastname: Han
authors.forename: Renxi
authors.initials: R
authors.lastname: Wang
authors.forename: Guojiang
authors.initials: G
authors.lastname: Chen
authors.forename: Ruonan
authors.initials: R
authors.lastname: Xu
authors.forename: He
authors.initials: H
authors.lastname: Xiao
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.forename: Shaoxia
authors.initials: S
authors.lastname: Geng
authors.forename: Yurong
authors.initials: Y
authors.lastname: Li
authors.forename: Xinying
authors.initials: X
authors.lastname: Li
authors.forename: Jianan
authors.initials: J
authors.lastname: Wang
authors.forename: Jiannan
authors.initials: J
authors.lastname: Feng
authors.forename: Niels C
authors.initials: NC
authors.lastname: Riedemann
authors.forename: Renfeng
authors.initials: R
authors.lastname: Guo
authors.forename: Beifen
authors.initials: B
authors.lastname: Shen
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001202:Ascitic Fluid / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001769:Blood / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D001773:Blood Cells / Q000187:drug effects / Q000378:metabolism; D054360:Chemokine CXCL1 / Q000235:genetics; D015936:Complement C5a / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D004195:Disease Models, Animal; D048168:Escherichia coli K12 / Q000276:immunology; D015870:Gene Expression / Q000235:genetics / Q000276:immunology; D006098:Granulocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D018805:Sepsis / Q000097:blood / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D051193:Toll-Like Receptors / Q000819:agonists
chemical_list: D000911:Antibodies, Monoclonal; D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; D016209:Interleukin-8; D008070:Lipopolysaccharides; D051193:Toll-Like Receptors; D015936:Complement C5a; D020928:Mitogen-Activated Protein Kinases