title: [Interleukin-17 contributes to the macrophage secretion of interleukin-27 in a murine model of viral myocarditis].
abstract: OBJECTIVE
  Interleukin-27 (IL-27) has been reported to reduce the levels of interleukin-17 (IL-17) and alleviate the severity of experimental autoimmune myocarditis. IL-17, an important tissue-protective cytokine in viral myocarditis (VMC), has been reported to increase synovial expression of IL-27 in rheumatoid arthritis. However, the influence of IL-17 on IL-27 expression in murine model of VMC remains unknown.
  
  
  METHODS
  Wild-type (WT) and IL-17A-deficient (IL-17A(-/-)) mice on the BALB/c background were intraperitoneally (i.p) injected with coxsackievirus B3 (CVB3) for establishing VMC models. Cardiac tissue was obtained on day 7 after CVB3 injection. Myocardial histopathologic changes were observed by hematoxylin-eosin (HE) stained myocardial sections.Expression of IL-27 in heart and serum was measured by real-time reverse transcription-polymerase chain reaction (RT-PCR) and enzyme linked immunosorbent assay (ELISA), respectively. Furthermore, splenic lymphocytes and peritoneal macrophages were purified 1 week after injection from WT mice.Isolated lymphocytes were cultured in the presence of different concentrations (0 and 25 ng/ml) of recombinant IL-17 (rIL-17) for 24 h. Macrophages were cultured with different concentrations of rIL-17 (0 and 10 ng/ml) for 48 h.IL-27 mRNA expression of cultured cells was assayed by RT-PCR, and their protein level in the culture supernatant was measured by ELISA.
  
  
  RESULTS
  Compared with WT mice, significantly less cardiac inflammation was evidenced in the heart of IL-17A-/- mice (0.9 ± 0.3 vs.1.9 ± 0.5) , relative cardiac IL-27 p28 mRNA expressions (1.11 ± 0.24 vs.3.1 ± 0.8) and serum IL-27 protein[(72 ± 18) pg/ml vs.(95 ± 25) pg/ml] were also significantly lower in IL-17A-/- mice (all P < 0.05).In the culture lymphocytes, the relative mRNA (1.02 ± 0.13 vs.1.32 ± 0.21) and protein [(49 ± 9) pg/ml vs.(52 ± 11) pg/ml]expressions of IL-27 p28 and were similar post treatment with 0 and 25 ng/ml rIL-17 (all P > 0.05). Compared with 0 ng/ml rIL-17 culture with macrophages, higher relative mRNA (8.5 ± 3.1 vs.2.2 ± 0.7) and protein [(368 ± 95) pg/ml vs.(150 ± 38) pg/ml] expressions of IL-27 p28 were detected in 10 ng/ml rIL-17 group (all P < 0.05).
  
  
  CONCLUSIONS
  Our data indicates that cytokine IL-17 may contribute to the secretion of IL-27 in VMC mice.Furthermore, macrophages but not lymphocytes may be the important IL-27-producing immune cells and major target cells for IL-17. Thus,IL-27 and IL-17 might be actively involved in the pathogenesis of VMC.
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Guangxi Medical University, Guangxi Cardiovascular Institute, Nanning 530021, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Kong
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Guangxi Medical University, Guangxi Cardiovascular Institute, Nanning 530021, China.
authors.forename: Mengsha
authors.initials: M
authors.lastname: Gao
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Guangxi Medical University, Guangxi Cardiovascular Institute, Nanning 530021, China.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Guangxi Medical University, Guangxi Cardiovascular Institute, Nanning 530021, China.
authors.forename: Xiaofen
authors.initials: X
authors.lastname: Pan
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Guangxi Medical University, Guangxi Cardiovascular Institute, Nanning 530021, China.
authors.forename: Wenying
authors.initials: W
authors.lastname: Lai
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Guangxi Medical University, Guangxi Cardiovascular Institute, Nanning 530021, China. Email: wucna65@163.com.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Wu
mesh_terms: D000818:Animals; D003384:Coxsackievirus Infections / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D020381:Interleukin-17 / Q000276:immunology*; D064094:Interleukin-27 / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000276:immunology* / Q000378:metabolism
chemical_list: D020381:Interleukin-17; D064094:Interleukin-27