Differential regulation of collagen, glycosaminoglycan, fibronectin, and collagenase activity production in cultured human adult dermal fibroblasts by interleukin 1-alpha and beta and tumor necrosis factor-alpha and beta

AbstractIn order to clarify the role played by immunologically derived cytokines in dermal connective tissue synthesis and degradation, we investigated the effect of human recombinant (hu-r) interleukin (IL) 1-alpha and beta, hu-r tumor necrosis factor (TNF)-alpha and beta, hu-r IL 2, and hu-r granulocyte-macrophage colony-stimulating factor (GMCSF) on the production of collagen, glycosaminoglycan, fibronectin, and collagenase activity by three lines of cultured human adult dermal fibroblasts. Our results show that 24–72 h treatment of confluent fibroblast cultures with IL 1-alpha or beta or TNF-alpha or beta causes concentration (1 to 1 × 104 U/ml) dependent increases in collagen, glycosaminoglycan, and collagenase activity production, but decreases in fibronectin production. In contrast, treatment with IL 2 and GM-CSF had no effect on fibroblast functions. The data show that IL 1-alpha and beta and TNF-alpha and beta differentially regulate fibroblast functions, and that increases in catabolic functions like collagenase activity production are more than tenfold greater than increases in anabolic functions like collagen production. When these results are considered along with other reports, they suggest that IL 1 and TNF may play predominately a catabolic role in situ during dermal fibrotic responses by directly inhibiting fibronectin production and indirectly causing the degradation of collagen and glycosaminoglycan by significantly increasing dermal fibroblast elaboration of collagenase and proteoglycanase activities