Stimulation of hyaluronan synthesis by interleukin-1β involves activation of protein kinase C βII in fibroblasts from patients with Graves' ophthalmopathy
✍ Scribed by Yi-Kuei Wong; Kam-Tsun Tang; Jiahn-Chun Wu; Jeng-Jong Hwang; Hwai-Shi Wang
- Publisher
- John Wiley and Sons
- Year
- 2001
- Tongue
- English
- Weight
- 195 KB
- Volume
- 82
- Category
- Article
- ISSN
- 0730-2312
- DOI
- 10.1002/jcb.1118
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✦ Synopsis
Abstract
Hyaluronan accumulation in the retroorbital connective tissue is one of the pathological features of Graves' ophthalmopathy. Interleukin‐1β (IL‐1β) 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‐1β‐induced hyaluronan synthesis was significantly inhibited by pretreatment of the cells with two protein kinase C (PKC) inhibitors, chlerythrine chloride and H‐7. In addition, treatment with phorbol 12‐myristate 13‐acetate (PMA), a direct PKC activator, also resulted in increased hyaluronan production. IL‐1β‐ or PMA‐stimulated hyaluronan synthesis was blocked by the protein synthesis inhibitor, cycloheximide. Moreover, the intracellular Ca^2+^ concentration of the orbital fibroblasts was also involved in the IL‐1β 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^2+^‐dependent PKC signal transduction pathway plays an important role in the IL‐1β‐induced hyaluronan synthesis. Moreover, IL‐1β treatment resulted in increased PKC activity and the rapid translocation of PKC βII from the cytoplasm to the plasma membrane. These results indicate that cytosolic Ca^2+^ and PKC βII are involved in IL‐1β‐induced hyaluronan synthesis in cultured orbital fibroblasts from patients with Graves' ophthalmopathy. J. Cell. Biochem. 82: 58–67, 2001. © 2001 Wiley‐Liss, Inc.