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M Tavolato, R Cortivo, AG Secchi, G Abatangelo, A Leonardi; Th2 Cytokines Stimulate Collagen Production and Modify MMP-1 and TIMP-1 Balance in Conjunctival Fibroblasts . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2256.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To identify if cytokines involved in chronic allergic conjunctival disorders may affect collagen production and tissue remodeling. Methods: Conjunctival fibroblast cultures were challenged with different concentrations of human recombinant interleukin (IL)-4, IL-13, interferon gamma (INFγ) and tumor necrosis factor alfa (TNFα). Procollagen I (PIP) and III (PIIIP), metalloproteinase (MMP)-1, MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1 were measured in supernatants and their respective messenger RNA (mRNA) was evaluated by RT-PCR. Collagenase and gelatinase activity were measured by the MMP-1 and-9 activity assay. Results: IL-4 and IL-13 (10ng/ml) significantly increased PIP production compared to non-stimulated cells while INFγ elicited the opposite effect both at protein and mRNA levels. Both IL-4 and IL-13 significantly decreased MMP-1 and increased TIMP-1 production, activity and expression, while TNFα increased MMP-1 and MMP-9. The TIMP-1/MMP-1 ratio was increased by both IL-4 and IL-13 treatment. Conclusion: IL-4 and IL-13 increased collagen production and modified the equilibrium between MMP-1 and its inhibitor, TIMP-1. These effects are partially opposed by those of INFγ. TNFα did not affect collagen production but did increased MMP expression and activity.
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