SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION-1 IN HUMAN MUSCLE - IMPLICATIONS IN INFLAMMATORY MYOPATHIES

Polymyositis (PM) and dermatomyositis (DM) are two major and distinct inflammatory myopathies. Cytokines, implicated in the immune process, have been recognized in the muscle tissue from PM and DM patients, but their functional in situ role has not been identified. We analyzed th e expression of the signal transducer and activator of transcription 1 (STAT1), a molecule whose up-regulation indicates the interaction of cytokines, or growth factors, with their target receptors in muscle fi bers and inflammatory infiltrates in PM and DM. An immunohistochemical analysis was performed using monoclonal antibodies to STAT1 in 57 mus cle biopsies from 10 patients with DM, 10 with PM, and 37 controls. Th e profile of STAT1 up-regulation was also investigated in cultured mus cle stimulated by interferon-gamma, epidermal growth factor, platelet- derived growth factor, and interleukin-2, using semiquantitative polym erase chain reaction and Western blot. High STAT1 expression was obser ved in many perifascicular atrophic muscle fibers from DM patients in 10/10 biopsies. In contrast, only a few muscle fibers undergoing necro sis were STAT1 positive in 2/10 patients with PM and in 2/37 controls. STAT1 reactivity was noted in most cells of the infiltrates in DM, PM , and controls. In vitro, STAT1 was stimulated by interferon-gamma but not by the other molecules studied. These results suggest that in DM, but not in PM, there is distinctive functional local cytokine activit y able to increase STAT1 expression in muscle fibers. As interferon-ga mma specifically activates STAT1 in vitro, this cytokine in conjunctio n with ischemia is probably involved in perifascicular muscle fiber pa thology in DM.