Title of article :
Regulation of IL-8 production by complement-activated product, C5a, in vitro and in vivo during sepsis
Author/Authors :
Wang، نويسنده , , Liyan and Han، نويسنده , , Gencheng and Wang، نويسنده , , Renxi and Chen، نويسنده , , Guojiang and Xu، نويسنده , , Ruonan and Xiao، نويسنده , , He and Li، نويسنده , , Xia and Geng، نويسنده , , Shaoxia and Li، نويسنده , , Yurong and Li، نويسنده , , Xinying and Wang، نويسنده , , Jianan and Feng، نويسنده , , Jiannan and Riedemann، نويسنده , , Niels C. and Guo، نويسنده , , Renfeng and Shen، نويسنده , , Beifen and Li، نويسنده ,
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 Escherichia coli, 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.
Keywords :
MAPK , C5a , IL-8 , TLR agonists , Sepsis
