RGD Reference Report - Regulatory role of C5a in LPS-induced IL-6 production by neutrophils during sepsis. - Rat Genome Database

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Regulatory role of C5a in LPS-induced IL-6 production by neutrophils during sepsis.

Authors: Riedemann, NC  Guo, RF  Hollmann, TJ  Gao, H  Neff, TA  Reuben, JS  Speyer, CL  Sarma, JV  Wetsel, RA  Zetoune, FS  Ward, PA 
Citation: Riedemann NC, etal., FASEB J. 2004 Feb;18(2):370-2. Epub 2003 Dec 19.
RGD ID: 1600599
Pubmed: PMID:14688199   (View Abstract at PubMed)
DOI: DOI:10.1096/fj.03-0708fje   (Journal Full-text)

Experimental sepsis in rodents occurring after cecal ligation/puncture (CLP) is associated with excessive complement activation and a systemic inflammatory response. The proinflammatory mediator IL-6 has recently been shown to be an important inducer of the C5a receptor (C5aR) during sepsis. We now provide evidence that serum IL-6 production during sepsis in rats was reduced in neutrophil-depleted animals and that absence of C5aR in mice as well as antibody-blockade of C5a in rats significantly reduced serum levels of IL-6 during sepsis. Lipopolysaccharide (LPS)-induced production in vitro of IL-6 by neutrophils was significantly enhanced in the co-presence of C5a, likely due to transcriptional up-regulation of IL-6. Production of IL-6 in neutrophils by LPS was NF-kappaB dependent (but not on the presence of p50) and dependent on phosphorylation of p38-mitogen activated protein kinase (MAPK) as well as p44/p42 MAPK (ERK1/2) but not on phosphorylation of c-Jun N-terminal kinases (JNK1/2). C5a stimulation of neutrophils elicited a rapid phosphorylation of ERK1/2 and p38 MAPK. Accordingly, we suggest that induction of IL-6 after CLP is neutrophil and C5a/C5aR dependent, likely due to the ability of C5a to cause activation of ERK1/2 and p38 MAPK signaling pathways.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
C5RatSepsis  IDA  RGD 
C5HumanSepsis  ISOC5 (Rattus norvegicus) RGD 
HcMouseSepsis  ISOC5 (Rattus norvegicus) RGD 

Objects Annotated

Genes (Rattus norvegicus)
C5  (complement C5)

Genes (Mus musculus)
Hc  (hemolytic complement)

Genes (Homo sapiens)
C5  (complement C5)


Additional Information