[Possible mechanism for regulation of inflammatory responses with the S100A8/A9 protein].
We have described a possible mechanism for the regulation of excessive inflammatory responses with S100A8/A9 protein in damaged rat livers. Recombinant human S100A8(r-S100A8) and S100A9 (r-S100A9) were expressed in E. coli cells, and their heterodimer (r-S100A8/A9) with 90% approximate purity was also prepared successfully. The effect of the r-S100A8/A9 on suppression of acute inflammatory changes in rat livers with LPS-induced damage was microscopically observed. Indeed, the liver damage diminished as the dose of the r-S100A8/A9 increased, and the minimum requirement of the protein was estimated to be 1,000 microg/rat in this study. Observation of superoxide anions was positively observed in control rats treated with LPS alone, but almost not in the livers of rats treated with the r-S 100A8/A9 1h after injection of LPS. This fact strongly suggests that the r-S100A8/A9 could indirectly suppress production of such internal oxidants according to unknown pathway (s) in acute inflammation. Expression of mRNAs of several kinds of inflammatory cytokines, such as TNF-alpha, IL-6 and IL-1beta, was also significantly suppressed, which was of much note. Therefore, the possibility that the r-S100A8/A9 partly inhibits the process of signal transduction of inflammatory responses in the immunological cells leading to down regulation of inflammatory changes in vivo was suggested in this study. Conclusively, S100A8/A9 is not necessarily an inflammatory-induced factor, and preferably effective on suppression of excessive inflammatory reaction in vivo dose-dependently, although the mechanism is still unclear.
Namura
Tomoyo
T
Arai
Satoshi
S
Koike
Akiko
A
Yamada
Sachiko
S
Totani
Masayuki
M
Ikemoto
Masaki
M
D000208:Acute Disease; D000818:Animals; D040501:Calgranulin A / Q000008:administration & dosage*; D040502:Calgranulin B / Q000008:administration & dosage*; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008264:Macrophages; D008297:Male; D009504:Neutrophils; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism
D040501:Calgranulin A; D040502:Calgranulin B; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D013481:Superoxides