Increased IL‐15 production of muscle cells in polymyositis and dermatomyositis

• Published in: International immunology 2002-08, Vol.14 (8), p.917-924
• Main Authors: Sugiura, Tomoko, Harigai, Masayoshi, Kawaguchi, Yasushi, Takagi, Kae, Fukasawa, Chikako, Ohsako‐Higami, Satomi, Ohta, Shuji, Tanaka, Michi, Hara, Masako, Kamatani, Naoyuki
• Format: Article
• Language: English
• Subjects: Animals; Case-Control Studies; Cell Line; Cells, Cultured; Cytokines - pharmacology; dermatomyositis; Dermatomyositis - genetics; Dermatomyositis - immunology; Gene Expression; Humans; IL‐15; Immunohistochemistry; Inflammation Mediators - metabolism; Interleukin-15 - biosynthesis; Interleukin-15 - genetics; Lipopolysaccharides - pharmacology; Lymphocyte Activation; Mice; muscle cells; Myoblasts, Skeletal - drug effects; Myoblasts, Skeletal - immunology; polymyositis; Polymyositis - genetics; Polymyositis - immunology; RNA, Messenger - genetics; RNA, Messenger - metabolism; T-Lymphocytes - immunology
• ISSN: 0953-8178; 1460-2377; 1460-2377
• DOI: 10.1093/intimm/dxf062

In polymyositis (PM)/dermatomyositis (DM), various cytokines, especially macrophage‐derived cytokines such as IL‐1α, IL‐1β and tumor necrosis factor (TNF)‐α, are expressed in the inflammatory foci. We previously reported that IL‐15, a novel cytokine with a biological activity similar to that of IL‐2, is expressed in muscle cells in PM/DM. In the present study, we set out to investigate the regulation of IL‐15 in cultured myoblasts. Myoblasts constitutively produced a low level of IL‐15 and the production was augmented by stimulation with IFN‐γ, IL‐1α, IL‐1β, TNF‐α or lipopolysaccharide (LPS) in a dose‐dependent manner. These stimuli also enhanced the expression of IL‐15 mRNA. About 30–40% of IL‐15 was detected intracellularly, while the rest was released into the culture supernatant. Immunohistochemical staining revealed that intracellular IL‐15 was localized in the perinuclear area of the cytoplasm in the myoblasts. Despite the considerable amounts of intracellular IL‐15, the myoblasts predominantly expressed authentic IL‐15 mRNA isoform. This isoform generates IL‐15 with long signal peptide preprotein, which is all to be secreted. The biological activity of IL‐15 secreted from the myoblasts was examined using an IL‐15‐dependent murine T cell line, CTLL‐2. Culture supernatants of the myoblasts induced a proliferative response of CTLL‐2 and this was specifically inhibited by anti‐IL‐15 antibody. These results suggest that inflammatory stimuli induce the production of IL‐15 in the muscle cells in PM/DM, and IL‐15 may contribute to the immunopathogenesis by augmenting recruitment and activation of the infiltrating T cells. Blocking of IL‐15 production might be of therapeutic value in PM/DM.