Stimulation of collagen and glycosaminoglycan production in cultured human adult dermal fibroblasts by recombinant human interleukin 6.
Interleukin (IL) 6 is a pleiotropic cytokine synthesized by fibroblasts in response to many stimuli, including IL-1 beta. To evaluate the possibility that previously observed stimulation of fibroblast biosynthetic functions by IL-1 beta may be mediated by autocrine IL-6, we investigated the effect of recombinant human (rh) IL-6 on the connective tissue-related biosynthetic functions of three lines of cultured human adult dermal fibroblasts. We found that rhIL-6 mimicked some of the activities of IL-1 beta, as 24-96-h treatment of confluent fibroblast cultures with rhIL-6 caused concentration (10 to 1000 ng/ml)-dependent increases in the production of collagen and the glycosaminoglycans (GAG), hyaluronic acid and chondroitin-4/6-sulfates, but had little effect on fibronectin or total protein production. Although the effective stimulating concentrations of IL-6 were within the range (approximately 100 ng/ml) we found produced by rhIL-1 beta-treated fibroblast cultures, rhIL-1 beta at 0.2-1.0 ng/ml induced significantly greater amounts of collagen and GAG than the maximum effective concentrations of IL-6. Moreover, an anti-rhIL-6 antibody, which effectively neutralized the fibroblast-stimulating activities of rhIL-6, only fractionally blocked the fibroblast-stimulating actions of rhIL-1 beta, suggesting autocrine IL-6 only partially mediates the effects of IL-1 beta on fibroblasts. Conversely, the fibroblast-stimulating effects of rhIL-6 are unlikely due to autocrine IL-1 beta, as an anti-rhIL-1 beta antibody had only minimal inhibitory action on rhIL-6-treated fibroblast cultures. Overall these results suggest that IL-6 could function as a paracrine/autocrine regulator of dermal fibrotic repair.
Department of Dermatology, University of California, Davis School of Medicine.
M R
MR
Duncan
B
B
Berman
D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006025:Glycosaminoglycans / Q000096:biosynthesis*; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology / Q000494:pharmacology; D015850:Interleukin-6 / Q000276:immunology / Q000494:pharmacology*; D014176:Protein Biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D012867:Skin / Q000187:drug effects / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D006025:Glycosaminoglycans; D007375:Interleukin-1; D015850:Interleukin-6; D011994:Recombinant Proteins; D003094:Collagen