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 degradi ng enzymes in cultured primary pterygium body fibroblasts activated by cyto kines and growth factors potentially derived from ocular surface epithelial cells and tears. METHODS. EGF, TGF-alpha, PDGF-BB, IL-1 beta, bFGF, TGF-beta 1, TNF-alpha, o r IL-6 were added at 10 ng/ml to early passaged primary pterygium body fibr oblasts (PBF) or normal human conjunctival fibroblasts (HJF) in a serum-fre e medium. Expression of transcripts and proteins of MMP-1, MMP-2, MMP-3, MM P-9, TIMP-1, TIMP-2, and uPA was determined by Northern hybridization, ELIS A, and Western blotting, respectively. Gelatin and casein zymographies were performed in their serum-free conditioned media with or without enzyme inh ibitors to determine the activity of MMP-2 and -3, respectively. RESULTS. IL-1 beta and TNF-alpha dramatically increased the mRNA and protei n 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. E GF and TGF-alpha also upregulated MMP-3 in PBF when compared to HJF. The tr anscript levels of MMP-2 were high but stable for the two cell types regard less 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 expre ssed in either of these two types of fibroblasts. Both IL-1 beta and TNF-al pha induced a significant decrease in uPA expression in PBF, whereas bFGF i nduced a slight increase in both HJE and PBF. CONCLUSIONS. Chronic inflammatory stimulation by IL-1 beta and TNF-alpha, w hich potentially can be derived from the ocular surface and tears, may be r esponsible for increased expression of MMPs in cultured PBF. These data hav e clinical implications on progression of pterygium and recurrence associat ed with incomplete excision of primary PBF under the influence of ocular su rface inflammation. Suppression of intraoperative and postoperative inflamm ation may be a new strategy to prevent pterygium recurrence.