{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T20:58:38Z","timestamp":1758401918499},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2001,4,10]],"date-time":"2001-04-10T00:00:00Z","timestamp":986860800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2001,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hyaluronan accumulation in the retroorbital connective tissue is one of the pathological features of Graves' ophthalmopathy. Interleukin\u20101\u03b2 (IL\u20101\u03b2) is known to stimulate hyaluronan synthesis in orbital fibroblasts. In the present study, the intracellular signal transduction pathways involved in this stimulatory effect were investigated in cultured human retroorbital fibroblasts from patients with Graves' ophthalmopathy. IL\u20101\u03b2\u2010induced hyaluronan synthesis was significantly inhibited by pretreatment of the cells with two protein kinase C (PKC) inhibitors, chlerythrine chloride and H\u20107. In addition, treatment with phorbol 12\u2010myristate 13\u2010acetate (PMA), a direct PKC activator, also resulted in increased hyaluronan production. IL\u20101\u03b2\u2010 or PMA\u2010stimulated hyaluronan synthesis was blocked by the protein synthesis inhibitor, cycloheximide. Moreover, the intracellular Ca<jats:sup>2+<\/jats:sup> concentration of the orbital fibroblasts was also involved in the IL\u20101\u03b2 induced transduction pathway, the effect being completely inhibited by BAPTA, an internal calcium chelator. In addition, A23187, a calcium ionophore, increased hyaluronan synthesis in unstimulated cells. These results suggest that the Ca<jats:sup>2+<\/jats:sup>\u2010dependent PKC signal transduction pathway plays an important role in the IL\u20101\u03b2\u2010induced hyaluronan synthesis. Moreover, IL\u20101\u03b2 treatment resulted in increased PKC activity and the rapid translocation of PKC \u03b2II from the cytoplasm to the plasma membrane. These results indicate that cytosolic Ca<jats:sup>2+<\/jats:sup> and PKC \u03b2II are involved in IL\u20101\u03b2\u2010induced hyaluronan synthesis in cultured orbital fibroblasts from patients with Graves' ophthalmopathy. J. Cell. Biochem. 82: 58\u201367, 2001. \u00a9 2001 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcb.1118","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T20:35:44Z","timestamp":1030307744000},"page":"58-67","source":"Crossref","is-referenced-by-count":16,"title":["Stimulation of hyaluronan synthesis by interleukin\u20101\u03b2 involves activation of protein kinase C \u03b2II in fibroblasts from patients with Graves' 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