Regulation of IL-8 production by complement-activated product, C5a, in vitro and in vivo during sepsis.
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.
Wang
Liyan
L
Department of Molecular Immunology, Institute of Basic Medical Sciences, Taiping Road, No. 27, Beijing 100850, People's Republic of China.
Han
Gencheng
G
Wang
Renxi
R
Chen
Guojiang
G
Xu
Ruonan
R
Xiao
He
H
Li
Xia
X
Geng
Shaoxia
S
Li
Yurong
Y
Li
Xinying
X
Wang
Jianan
J
Feng
Jiannan
J
Riedemann
Niels C
NC
Guo
Renfeng
R
Shen
Beifen
B
Li
Yan
Y
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
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