Regulation of collagenase, stromelysin, and urokinase-type plasminogen activator in primary pterygium body fibroblasts by inflammatory cytokines.

PURPOSE To examine the expression patterns of extracellular matrix degrading enzymes in cultured primary pterygium body fibroblasts activated by cytokines and growth factors potentially derived from ocular surface epithelial cells and tears. METHODS EGF, TGF-alpha, PDGF-BB, IL-1beta, bFGF, TGF-beta1, TNF-alpha, or IL-6 were added at 10 ng/ml to early passaged primary pterygium body fibroblasts (PBF) or normal human conjunctival fibroblasts (HJF) in a serum-free medium. Expression of transcripts and proteins of MMP-1, MMP-2, MMP-3, MMP-9, TIMP-1, TIMP-2, and uPA was determined by Northern hybridization, ELISA, and Western blotting, respectively. Gelatin and casein zymographies were performed in their serum-free conditioned media with or without enzyme inhibitors to determine the activity of MMP-2 and -3, respectively. RESULTS IL-1beta and TNF-alpha dramatically increased the mRNA and protein expression of MMP-1 and MMP-3 in cultured PBF when compared to normal HJF and to their nonstimulated counterparts cultured in a serum-free medium. EGF and TGF-alpha also upregulated MMP-3 in PBF when compared to HJF. The transcript levels of MMP-2 were high but stable for the two cell types regardless of the cytokine treatment. Both TIMP-1 and TIMP-2 expressions were not influenced by the cell type or the cytokine treatment. MMP-9 was not expressed in either of these two types of fibroblasts. Both IL-1beta and TNF-alpha induced a significant decrease in uPA expression in PBF, whereas bFGF induced a slight increase in both HJF and PBF. CONCLUSIONS Chronic inflammatory stimulation by IL-1beta and TNF-alpha, which potentially can be derived from the ocular surface and tears, may be responsible for increased expression of MMPs in cultured PBF. These data have clinical implications on progression of pterygium and recurrence associated with incomplete excision of primary PBF under the influence of ocular surface inflammation. Suppression of intraoperative and postoperative inflammation may be a new strategy to prevent pterygium recurrence.