Regulation of IL-8 production by complement-activated product, C5a, in vitro and in vivo during sepsis

Liyan Wang; Gencheng Han; Renxi Wang; Guojiang Chen; Ruonan Xu; He Xiao; Xia Li; Shaoxia Geng; Yurong Li; Xinying Li; Jianan Wang; Jiannan Feng; Niels C Riedemann; Renfeng Guo; Beifen Shen; Yan Li

doi:10.1016/j.clim.2010.05.012

Regulation of IL-8 production by complement-activated product, C5a, in vitro and in vivo during sepsis

Clin Immunol. 2010 Oct;137(1):157-65. doi: 10.1016/j.clim.2010.05.012. Epub 2010 Jun 29.

Authors

Liyan Wang¹, Gencheng Han, Renxi Wang, Guojiang Chen, Ruonan Xu, He Xiao, Xia Li, Shaoxia Geng, Yurong Li, Xinying Li, Jianan Wang, Jiannan Feng, Niels C Riedemann, Renfeng Guo, Beifen Shen, Yan Li

Affiliation

¹ Department of Molecular Immunology, Institute of Basic Medical Sciences, Taiping Road, No. 27, Beijing 100850, People's Republic of China.

PMID: 20591742
DOI: 10.1016/j.clim.2010.05.012

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Monoclonal / immunology
Antibodies, Monoclonal / pharmacology
Ascitic Fluid / cytology
Ascitic Fluid / drug effects
Ascitic Fluid / metabolism
Blood / drug effects
Blood / metabolism
Blood / microbiology
Blood Cells / drug effects
Blood Cells / metabolism
Chemokine CXCL1 / genetics
Complement C5a / immunology
Complement C5a / metabolism*
Complement C5a / pharmacology
Disease Models, Animal
Escherichia coli K12 / immunology
Gene Expression / genetics
Gene Expression / immunology
Granulocytes / drug effects
Granulocytes / metabolism
Humans
Interleukin-8 / metabolism*
Lipopolysaccharides / pharmacology
Male
Mice
Mice, Inbred C57BL
Mitogen-Activated Protein Kinases / antagonists & inhibitors
Mitogen-Activated Protein Kinases / metabolism
Monocytes / drug effects
Monocytes / metabolism
Phosphorylation / drug effects
Sepsis / blood
Sepsis / metabolism*
Signal Transduction / drug effects
Toll-Like Receptors / agonists

Substances

Antibodies, Monoclonal
Chemokine CXCL1
Cxcl1 protein, mouse
Interleukin-8
Lipopolysaccharides
Toll-Like Receptors
Complement C5a
Mitogen-Activated Protein Kinases