Intrinsic function of S100A8/A9 complex as an anti-inflammatory protein in liver injury induced by lipopolysaccharide in rats.
BACKGROUND
We hypothesized that the S100A8/A9 complex is effective in the suppression of acute inflammatory changes.


METHODS
To clarify such a functional role of the S100A8/A9 complex in acute inflammatory disorder, the complex purified from human leukocytes (approx. 1 mg) was intraperitoneally injected into rats 1.0 or 3.5 h after an injection of lipopolysaccharide (LPS).


RESULTS
The serum concentrations of interleukin-6 (IL-6) and nitric oxide (NOx) were significantly decreased in the treated rats. Conversely, when anti-S100A8/A9 complex IgG was injected into the tail blood vessel of a rat 1.0 h after the injection of LPS, the serum concentration of IL-6 increased slightly, indicating that the antibody immunoregulatorily blocked the activity of the complex as an anti-inflammatory protein in vivo. In addition, the S100A8/A9 complex bound non-specifically with interleukin-1beta (IL-1beta), IL-6 and TNF-alpha in vitro, suggesting that the complex could bind with these cytokines in vivo. A large number of endogenous S100A8/A9 complex-positive cells that accumulated in the inflamed region in the liver 6 h after the injection of LPS were microscopically observed, while apparent inflammatory changes were not found microscopically in other organs, such as the kidney, lung and spleen. In rats treated with the S100A8/A9 complex, neither acute inflammatory changes nor S100A8/A9 complex-positive cells were also observed microscopically in the liver tissue.


CONCLUSIONS
These findings suggest that the S100A8/A9 complex indirectly suppresses the overproduction of NOx from activated neutrophils and/or macrophages by neutralizing the activity of pro-inflammatory cytokines. Thus, the S100A8/A9 complex may play an important role in the suppression of acute inflammation by modulating the vital activity of pro-inflammatory cytokines in vivo.
Ikemoto
Masaki
M
Department of Laboratory Science, School of Health Sciences, Faculty of Medicine, Kyoto University, 53 Kawaharacho, Shogoin, Kyoto 606-8507, Japan. mmas@kuhp.kyoto-u.ac.jp
Murayama
Hiroshi
H
Itoh
Hiroshi
H
Totani
Masayuki
M
Fujita
Masatoshi
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D040501:Calgranulin A / Q000276:immunology*; D040502:Calgranulin B / Q000276:immunology*; D004195:Disease Models, Animal; D006505:Hepatitis / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects / Q000293:injuries*; D008297:Male; D046912:Multiprotein Complexes / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000911:Antibodies, Monoclonal; D040501:Calgranulin A; D040502:Calgranulin B; D018836:Inflammation Mediators; D015850:Interleukin-6; D008070:Lipopolysaccharides; D046912:Multiprotein Complexes; D009569:Nitric Oxide