Interleukin-17 contributes to the macrophage secretion of interleukin-27 in a murine model of viral myocarditis
10.3760/cma.j.issn.0253-3758.2014.05.017
- VernacularTitle:白细胞介素-17通过促进巨噬细胞分泌白细胞介素-27参与小鼠病毒性心肌炎的发生
- Author:
Qing KONG
1
;
Mengsha GAO
;
Yimin XUE
;
Xiaofen PAN
;
Wenying LAI
;
Weifeng WU
Author Information
1. 广西医科大学第一附属医院心内科广西心血管病研究所
- Keywords:
Myocarditis;
Interleukin-17;
Interleukin-27
- From:
Chinese Journal of Cardiology
2014;42(5):428-432
- CountryChina
- Language:Chinese
-
Abstract:
Objective Interleukin-27 (IL-27) has been reported to reduce the levels of interleukin17(IL-17) and alleviate the severity of experimental autoimmune myocarditis.IL-17,an important tissueprotective 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).Conclusion 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.