The effect of hyaluronic acid on interleukin-1-induced deregulation of collagen metabolism in cultured human skin fibroblasts.
Although hyaluronic acid (HA) has been used in the treatment of osteoarthritis for 30 years, the mechanism of its protective action on collagen metabolism disturbances in tissues during inflammation is not known. The present study was undertaken to evaluate the mechanism of Interleukin-1 (IL-1)-induced deregulation of collagen metabolism in cultured human skin fibroblast and the effect of HA on the process. In normal fibroblasts IL-1 strongly induced inhibition of collagen biosynthesis, while HA counteracted the process. The mechanism of this phenomenon was independent of prolidase activity, an enzyme that plays an important role in collagen biosynthesis at the post-translational level. Instead, IL-1 was found to inhibit the expression of insulin-like growth factor-I receptor (IGF-IR) and MAP kinases-ERK1 and ERK2, while HA was shown to counteract this process. Since insulin-like growth factor-I (IGF-I) is a most potent stimulator of collagen biosynthesis in fibroblasts the mechanism of IL-1-dependent inhibition of collagen biosynthesis may be related to inhibition of IGF-IR expression and signaling. The data suggest that hyaluronic acid protects collagen against IL-1-induced inhibition of biosynthesis of this protein in cultured human skin fibroblasts at the level of IGF-IR signaling.
Nawrat
P
P
Department of Medicinal Chemistry, Medical Academy of Białystok, Kilińskiego 1, 15-089 Białystok, Poland.
Surazyński
A
A
Karna
E
E
Pałka
J A
JA
D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis / Q000378:metabolism*; D004150:Dipeptidases / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology / Q000502:physiology*; D007375:Interleukin-1 / Q000494:pharmacology / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis; D015398:Signal Transduction; D012867:Skin / Q000166:cytology
D007375:Interleukin-1; D006820:Hyaluronic Acid; D003094:Collagen; D017526:Receptor, IGF Type 1; D020928:Mitogen-Activated Protein Kinases; D004150:Dipeptidases; C022449:proline dipeptidase