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JR Samples, J Choi, AM Miller, PA Knepper; Cytokine Induced Production of sCD44 in the Human Eye . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3956.
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Purpose:To evaluate whether cytokines known to be produced in the eye in response to specific stimuli induce the production of soluble CD44 (sCD44), a broadly distributed protein which binds hyaluronate, fibronectin, and laminin. Methods:Human trabecular meshwork (HTM) cell cultures and organ cultured ciliary body epithelium was obtained from young donors through the Oregon Lion's Eye Bank and protocols were approved by the institutional human subjects committee and conformed to the Declaration of Helsinki. Cells were grown in Dulbeco's media supplemented with 10% fetal calf serum and were harvested at passages 3 through 6. Treatments included 4 nG/ML human recombinant interleukin-1 alpha (IL1-a) and 10 nG/ML tumor necrosis factor alpha (TNFa). The effects of the cytokines were determined by ELISA, western blotting and dual-labeling immunofluorescence. Results:IL1-a increased sCD44 in the ciliary epithelial supernatant by greater than 6-fold (P<0.05) for paired, matched ciliary bodies and TNFa increased sCD44 in HTM cell cultures by about 2-fold. TNFa also increased matrix metalloproteinases 9 in the HTM cultures. Conclusion:IL1-a and TNFa are known to be present in the eye and increase in response to both laser treatment and inflammation and have direct effects upon the production of the matrix metalloproteinases and their inhibitors, which in turn regulate extracellular matrix (ECM) turnover. The effects of IL1-a and TNFa increasing sCD44 concentrations has profound implications for glaucoma since it suggests: 1) A new mechanism by which ECM components may be altered by the cytokines studied; 2) A mechanism by which trabecular cells may be destroyed in the inflammatory state (whether postoperative or due to uveitis, since sCD44 is toxic to trabecular cells; and 3) A regulatory mechanism for CD44 which may itself have an important role in glaucoma through interactions with TGF beta and other cytokines.
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