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(Investigative Ophthalmology and Visual Science. 2003;44:183-189.)
© 2003 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.02-0420
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Effects of Th2 Cytokines on Expression of Collagen, MMP-1, and TIMP-1 in Conjunctival Fibroblasts

Andrea Leonardi,1,2 Roberta Cortivo,3 Iva Fregona,1 Mario Plebani,2 Antonio G. Secchi,1 and Giovanni Abatangelo3

1From the Department of Neuroscience, Ophthalmology and Ocular Inflammation Unit; the 3Department of Histology, Microbiology and Medical Biotechnologies; and the 2Department of Laboratory Medicine, University of Padua, Padua, Italy.

PURPOSE. To determine whether cytokines involved in chronic allergic conjunctival disorders may affect formation of giant papillae and tissue remodeling.

METHODS. Conjunctival fibroblast cultures were challenged with different concentrations of human recombinant interleukin (IL)-4, IL-13, interferon (IFN)-{gamma} and tumor necrosis factor (TNF)-{alpha}. Procollagens I (PIP) and III (PIIIP), matrix metalloproteinase (MMP)-1 and -9, and tissue inhibitor of metalloproteinase (TIMP)-1 were measured in supernatants, and their respective mRNAs were evaluated by RT-PCR.

RESULTS. IL-4 and -13 (10 ng/mL) significantly increased production and expression of PIP compared with nonstimulated cells, whereas IFN-{gamma} elicited the opposite effect, at both the protein and mRNA levels. Both IL-4 and -13 significantly decreased production of MMP-1 and increased that of TIMP-1, whereas TNF-{alpha} increased production of MMP-1 and -9. Expression of MMP-1 was reduced by IL-4 and increased by the other tested cytokines, whereas expression of TIMP-1 was increased by all tested cytokines.

CONCLUSIONS. IL-4 and -13 increased production of collagen and modified the equilibrium between MMP-1 and its inhibitor, TIMP-1. These effects were partially opposed by IFN-{gamma} and TNF-{alpha}.




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