Mucosal production of complement C3 and serum amyloid A is differentially regulated in different parts of the gastrointestinal tract during endotoxemia in mice.
The effect of endotoxemia and sepsis on mucosal production of the acute-phase proteins complement component C3 and serum amyloid A (SAA) was studied in mice. In addition, the role of the proinflammatory cytokines tumor necrosis factor-alpha, interleukin (IL)(-1)beta, and IL-6 on mucosal C3 and SAA production was examined. Endotoxemia was induced by the subcutaneous injection of 250 microg/mouse of lipopolysaccharide. Control mice were injected with corresponding volumes of sterile saline solution. Sepsis was induced by cecal ligation and puncture, and sham-operated mice served as controls. Endotoxemia resulted in increased mucosal C3 levels in all parts of the gastrointestinal tract examined, from the stomach to the colon, with the most pronounced effects noticed in the proximal gastrointestinal tract. The influence of endotoxemia on mucosal SAA production was more differentiated with increased levels noted in the jejunum and ileum, and no changes seen in gastric and colonic mucosa. Sepsis resulted in similar changes in mucosal C3 and SAA levels as seen in endotoxemic mice, except that SAA levels were increased in colonic mucosa of septic mice. Among the cytokines, IL(-1)beta resulted in the most pronounced changes in mucosal acute-phase proteins. The increase in C3 and SAA levels in the mucosa of the small intestine during endotoxemia was partially blocked by IL(-1) receptor antagonist. The results suggest that endotoxemia is associated with increased mucosal C3 production in different parts of the gastrointestinal tract and increased SAA production in the mucosa of the small intestine. Mucosal acute-phase protein synthesis may, at least in part, be regulated by IL(-1)beta.
Wang
Q
Q
Department of Surgery, University of Cincinnati, and Shriners Burns Institute, Cincinnati, Ohio 45267-0558, USA.
Wang
J J
JJ
Fischer
J E
JE
Hasselgren
P O
PO
D000704:Analysis of Variance; D000818:Animals; D015152:Blotting, Northern; D003176:Complement C3 / Q000096:biosynthesis* / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology; D019446:Endotoxemia / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D004927:Escherichia coli Infections / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D018805:Sepsis / Q000378:metabolism*; D000685:Serum Amyloid A Protein / Q000096:biosynthesis* / Q000187:drug effects
D003176:Complement C3; D016207:Cytokines; D012333:RNA, Messenger; D000685:Serum Amyloid A Protein