Myoblasts produce IL-6 in response to inflammatory stimuli

Muscle fibers are the target of T cell-mediated cytotoxic reactions inpolymyositis and inclusion body myositis, while the success of myoblasttransplantation depends on the absence of an immune rejection against themyofibers. In order to study the behaviour of muscle cells in aninflammatory milieu, we investigated the production of IL-6 and itsmodulation, including the second messenger pathways controlling it, in invitro highly purified human myoblast cultures. We found that IL- 1beta,tumor necrosis factor (TNF)-alpha and lipopolysaccharide (LPS) stimulatedmyoblast IL-6 secretion in a dose- and time-dependent manner, whereasforskolin and cholera toxin did not. HA1004 at 10 microM did notsignificantly affect the IL-1beta- and TNF-alpha-induced IL-6 secretion,suggesting that cAMP and protein kinase A are not sufficient to stimulatethis process. To investigate the role of protein kinase C (PKC) in thissignal transduction, we employed the inhibitor calphostin C, and theactivators phorbol-12-myristate-13- acetate (PMA) and calcium ionophoreA23187. Calphostin C blocked IL-6 secretion, PMA had a small stimulatoryeffect and A23187 had no effect; moreover, PKC down-regulation by PMA didnot inhibit IL-1beta stimulation, while it reduced TNF-alpha stimulation.These data indicate that different PKC isoforms may be involved inTNF-alpha and IL-1beta signal transduction. Such a difference candistinguish the action of two traditionally 'overlapping' inflammatorycytokines. Our data suggest that muscle cells, like myoblasts, satellitecells and in vivo regenerating myofibers, may discriminate betweendifferent stimuli and produce IL-6 when activated in response to muscleinjury.