Suppression of inflammation in rat autoimmune myocarditis by S100A8/A9 through modulation of the proinflammatory cytokine network.
OBJECTIVE
S100A8/A9 is expressed in activated monocytes/macrophages and assumed to be heavily involved in the pathogenesis of acute inflammation. Although several studies have asserted that S100A8/A9 has a proinflammatory function, the exact biological function of S100A8/A9 is yet to be described. We examined the anti-inflammatory effects of S100A8/A9 on experimental autoimmune myocarditis (EAM) in rats.


RESULTS
Experimental autoimmune myocarditis was induced in Lewis rats by immunization with porcine cardiac myosin. The recombinant (R-) S100A8/A9 was injected intraperitoneally into EAM rats. R-S100A8/A9 attenuated the severity of myocarditis, as evidenced by echocardiographic and histological findings. In addition, we found that not only the mRNA expression of proinflammatory cytokines [interleukin (IL)-1beta, IL-6, and tumour necrosis factor (TNF)-alpha] in the myocardium, but also their serum concentrations were suppressed in EAM rats treated with R-S100A8/A9. Nuclear factor-kappa B expression in inflammatory cells was also suppressed in the treated rats. To elucidate the mechanistic function of S100A8/A9 on proinflammatory cytokines in vivo, we used an ELISA on the supernatant of homogenized heart tissue treated with R-S100A8/A9. The findings revealed high-affinity binding of R-S100A8/A9 with IL-1beta, IL-6, and TNF-alpha in the myocardium, suggesting the trapping of proinflammatory cytokines by R-S100A8/A9.


CONCLUSIONS
S100A8/A9 attenuates EAM through modulation of the proinflammatory cytokine network.
Otsuka
Kaoru
K
Department of Internal Medicine III, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki 569-8686, Japan.
Terasaki
Fumio
F
Ikemoto
Masaki
M
Fujita
Shuichi
S
Tsukada
Bin
B
Katashima
Takashi
T
Kanzaki
Yumiko
Y
Sohmiya
Koichi
K
Kono
Tatsuji
T
Toko
Haruhiro
H
Fujita
Masatoshi
M
Kitaura
Yasushi
Y
D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D040501:Calgranulin A / Q000627:therapeutic use*; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D008264:Macrophages / Q000378:metabolism; D008297:Male; D009205:Myocarditis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins; D016896:Treatment Outcome
D040501:Calgranulin A; D016207:Cytokines; D012333:RNA, Messenger; D011994:Recombinant Proteins