Interleukin-6 (IL6) is a potent smooth muscle mitogen which contributes to lung remodelling in asthma by augmenting smooth muscle deposition and sub-epithelial fibrosis. To investigate the signalling pathways responsible for these effects, we determined if IL6 could induce lung fibroblast-myofibroblast differentiation through two potentiators of vascular smooth muscle cell differentiation: the mammalian target of rapamycin (mTOR) and the peroxisome proliferator activated receptor-[gamma] (PPAR[gamma]). IL6 induced mTOR activity (aS6K1 T389 phosphorylation), PPAR[gamma]- driven reporter gene activity and cardiac asmooth muscle actin (aSMA) deposition in human lung fibroblasts. Each of these effects were abolished by the mTOR inhibitor, rapamycin, the PPAR[gamma]-specific antagonist T0070907 and were specified to IL6 using a blocking antibody against the IL6 receptor. Moreover, induction of mTOR activity by over-expression of its upstream G- protein, Rheb, significantly induced PPAR[gamma]-driven reporter gene expression and was not induced further by IL6. We conclude that IL6 promotes lung fibroblast-myofibroblast differentiation by inducing mTOR activation of PPAR[gamma].