BIDIMENSIONAL GEL-ELECTROPHORETIC ANALYSIS OF PROTEIN-SYNTHESIS AND RESPONSE TO INTERFERON-GAMMA IN CULTURED HUMAN DERMAL FIBROBLASTS

Densitometric analysis of [S-35]methionine-labeled dermal fibroblast p roteins by two-dimensional protein gel electrophoresis revealed that c ultures derived from abdominal wall and the anterior aspect of lower l eg skin exhibit different patterns of specific protein synthesis. More over, the response to interferon-gamma is dependent upon the anatomic site of culture derivation. Plasminogen activator inhibitor type-1 is expressed constitutively in fibroblasts from both sites. However, inte rferon-gamma (100 U/ml) treatment for 48 h resulted in an up-regulatio n of the polypeptide in leg cultures and a marked inhibition of expres sion in fibroblasts from the abdomen. A number of other protein spots became more or less abundant in cultures from the two sites following treatment with the cytokine. It would appear that dermal fibroblasts f rom the abdominal wall and leg differ intrinsically in regard to their protein synthetic repertoires and their responses to interferon-gamma . These findings may be relevant to the pathogenesis of Graves' dermop athy where the skin of the lower leg becomes infiltrated with glycosam inoglycans and other extracellular material.