title: Suppression of inflammation in rat autoimmune myocarditis by S100A8/A9 through modulation of the proinflammatory cytokine network.
abstract: 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.
authors.affiliation: Department of Internal Medicine III, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki 569-8686, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Otsuka
authors.forename: Fumio
authors.initials: F
authors.lastname: Terasaki
authors.forename: Masaki
authors.initials: M
authors.lastname: Ikemoto
authors.forename: Shuichi
authors.initials: S
authors.lastname: Fujita
authors.forename: Bin
authors.initials: B
authors.lastname: Tsukada
authors.forename: Takashi
authors.initials: T
authors.lastname: Katashima
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Kanzaki
authors.forename: Koichi
authors.initials: K
authors.lastname: Sohmiya
authors.forename: Tatsuji
authors.initials: T
authors.lastname: Kono
authors.forename: Haruhiro
authors.initials: H
authors.lastname: Toko
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Fujita
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kitaura
mesh_terms: 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
chemical_list: D040501:Calgranulin A; D016207:Cytokines; D012333:RNA, Messenger; D011994:Recombinant Proteins