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Mayumi Mohri, Peter S. Reinach, Atsuhiro Kanayama, Makoto Shimizu, Jackob Moskovitz, Tatsuhiro Hisatsune, Yusei Miyamoto; Suppression of the TNFα-Induced Increase in IL-1α Expression by Hypochlorite in Human Corneal Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2002;43(10):3190-3195.
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purpose. In response to injury, activated neutrophils release tumor necrosis factor (TNF)-α and myeloperoxidase (MPO). TNFα in turn causes human corneal epithelial cells to secrete interleukin (IL)-1α, whereas MPO results in formation of HClO/OCl−. The effect of HClO/OCl− on the expression of the IL-1α gene and protein is unknown. The current study was undertaken to examine in immortalized human corneal epithelial cells whether NaOCl alters TNFα-induced increases in expression of IL-1α gene and protein.
methods. Semiquantitative RT-PCR and ELISA characterized IL-1α gene and protein expression, respectively. TNFα-induced nuclear transfer of nuclear factor (NF)-κB was measured by electrophoretic mobility shift assay (EMSA). The α isoform of inhibitory protein κB (IκBα) was identified by Western blot analysis.
results. Exposure to NaOCl (0.75 mM) for 10 minutes caused suppression of TNFα-induced increases in IL-1α mRNA and protein, declines in NFκB nuclear transfer, and a modification of IκBα, based on a bandshift detected by Western blot analysis. Modified IκBα became resistant to TNFα-induced proteolysis. Methionine sulfoxide reductase A (MsrA, 10 μM) eliminated the NaOCl-induced IκBα bandshift.
conclusions. NaOCl oxidizes IκBα at methionine residues and thereby suppresses dissociation of IκBα from NFκB. Decreased dissociation could in turn suppress TNFα-induced activation of NFκB, resulting in declines in expression of IL-1α gene and protein. These effects suggest that release of HClO/OCl− in vivo by activated neutrophils may counterbalance TNFα-induced NFκB-dependent secretion if IL-1α and suppress an excessive inflammatory reaction.
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