Inhibitory effect of pentoxifylline on HLA-DR expression and glycosaminoglycan synthesis of retrobulbar fibroblasts induced by interferon gamma.
Glycosaminoglycan (GAG) accumulation produced by retroocular fibroblasts (REF) has been observed in patients with thyroid-associated ophthalmopathy (TAO). Various cytokines are able to express HLA-DR molecules and stimulate the REF to proliferate GAG and free oxygen radicals. Pentoxifylline (Ptx) is known to have complex immunomodulatory effects on production of cytokines including interferon gamma (IFN-gamma). Ptx has been assumed to inhibit the cytokine-induced production of GAG and HLA-DR expression. We wished to determine whether Ptx has an effect on the IFN-gamma induced HLA-DR expression and influences the spontaneous and cytokine-induced GAG synthesis of REF. REF derived from extraocular muscles of healthy subjects were cultured without and with IFN-gamma. The effect of Ptx on expression of HLA-DR molecules and the production of GAG by REF was determined. Glycosaminoglycan was measured by incorporation of (3H)glycosamine into GAG. HLA-DR expression was analysed by fluorescence activated cell sorter. IFN-gamma (50, 100 and 500 U/ml) induced an increase in expression of HLA-DR molecules of REF. Ptx was proved not to be toxic for cultured cells. This drug was able to dose-dependently inhibit HLA-DR expression of REF. Both spontaneous and IFN-gamma-induced GAG synthesis of REF was inhibited by Ptx (100, 500 and 1000 mg/l, respectively). Due to in vitro inhibitory effects, Ptx is potentially able to modify the antigen presentation and the GAG synthesis by REF and it might be a useful therapeutical drug in the treatment of TAO.
Balázs
C
C
III. Department of Medicine-Endocrinology, Kenézy Teaching Hospital, Debrecen, Hungary.
Kiss
E
E
Farid
N R
NR
D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000378:metabolism; D006025:Glycosaminoglycans / Q000096:biosynthesis*; D006684:HLA-DR Antigens / Q000032:analysis*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D010431:Pentoxifylline / Q000494:pharmacology*
D006025:Glycosaminoglycans; D006684:HLA-DR Antigens; D007371:Interferon-gamma; D010431:Pentoxifylline