Myoblasts produce IL-6 in response to inflammatory stimuli.
Muscle fibers are the target of T cell-mediated cytotoxic reactions in polymyositis and inclusion body myositis, while the success of myoblast transplantation depends on the absence of an immune rejection against the myofibers. In order to study the behaviour of muscle cells in an inflammatory milieu, we investigated the production of IL-6 and its modulation, including the second messenger pathways controlling it, in in vitro highly purified human myoblast cultures. We found that IL-1beta, tumor necrosis factor (TNF)-alpha and lipopolysaccharide (LPS) stimulated myoblast IL-6 secretion in a dose- and time-dependent manner, whereas forskolin and cholera toxin did not. HA1004 at 10 microM did not significantly affect the IL-1beta- and TNF-alpha-induced IL-6 secretion, suggesting that cAMP and protein kinase A are not sufficient to stimulate this process. To investigate the role of protein kinase C (PKC) in this signal transduction, we employed the inhibitor calphostin C, and the activators phorbol-12-myristate-13-acetate (PMA) and calcium ionophore A23187. Calphostin C blocked IL-6 secretion, PMA had a small stimulatory effect and A23187 had no effect; moreover, PKC down-regulation by PMA did not inhibit IL-1beta stimulation, while it reduced TNF-alpha stimulation. These data indicate that different PKC isoforms may be involved in TNF-alpha and IL-1beta signal transduction. Such a difference can distinguish the action of two traditionally 'overlapping' inflammatory cytokines. Our data suggest that muscle cells, like myoblasts, satellite cells and in vivo regenerating myofibers, may discriminate between different stimuli and produce IL-6 when activated in response to muscle injury.
Gallucci
S
S
Institute of General Pathology, Catholic University, Rome, Italy.
Provenzano
C
C
Mazzarelli
P
P
Scuderi
F
F
Bartoccioni
E
E
D000262:Adenylyl Cyclases / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis*; D009132:Muscles / Q000166:cytology / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000001:Calcimycin; D000262:Adenylyl Cyclases; D013755:Tetradecanoylphorbol Acetate