MODULATED RESPONSE TO CYTOKINES OF HUMAN WOUND-HEALING MYOFIBROBLASTSCOMPARED TO DERMAL FIBROBLASTS

Myofibroblasts play an important role in normal wound healing. They ar e present transiently during tissue repair. Their differentiation from fibroblasts and their role in granulation tissues are most likely to be modulated by cytokines. As these cells are derived from normal fibr oblasts, their responses to cytokines are assumed to be similar. Until mow, however, the difficulties in obtaining and maintaining normal hu man wound healing myofibroblasts in vitro have hampered comparison. Th e present study was designed to determine the effect of TGF-beta 1 and IFN-gamma, two cytokines known to modulate fibroblast morphology, on wound healing myofibroblasts and to compare it to fibroblasts. Morphol ogical and phenotypic changes were followed by light and electron micr oscopy (stress fibers) and immunofluorescence cytochemistry (alpha-SM actin). Functional parameters such as the capacity to synthesize colla gen and collagen gel contraction were studied. Both cytokines induced a strong modification of growth rate and phenotypic and morphological parameters in fibroblasts whereas collagen synthesis was slightly chan ged. Furthermore, TGF-beta 1 increased contractile capacity of fibrobl asts whereas IFN-gamma greatly decreased it. In myofibroblasts, TGF-be ta 1 and IFN-gamma did not induce any variation of morphology or growt h rate, Interestingly, a strong modulation of functional parameters wa s observed: collagen synthesis was highly modified and, as for fibrobl asts, the contractile capacity was altered. However, inhibition of con traction by IFN-gamma was irreversible in myofibroblasts but not in fi broblasts, These results suggest that fibroblastic cells show modulate d responses to cytokines according to their stage of differentiation d uring wound healing. (C) 1998 Academic Press.