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Biochem Biophys Res Commun. 2006 May 19;343(4):995-1001. Epub 2006 Mar 23.

IL-4 regulates COX-2 and PGE2 production in human non-small cell lung cancer.

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Lung Cancer Research Program of the Jonsson Comprehensive Cancer Center, and Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.


IL-4 is a type 2 cytokine that may mediate pleiotropic effects in the NSCLC microenvironment. Here, we investigated whether IL-4 regulates PGE(2) production in NSCLC cells. We found that IL-4 inhibited constitutive COX-2 expression and PGE(2) production in A427 and H2122 NSCLC cell lines, and also suppressed IL-1beta-induced COX-2 expression in A549 and RH2 NSCLC cell lines. COX-2 mRNA was decreased in response to IL-4, and promoter analysis indicated that IL-4 inhibited both constitutive and IL-1beta-induced COX-2 transcription. IL-4 inhibited IL-1beta-stimulated ERK phosphorylation, which may mediate the inhibition of IL-1beta-induced COX-2 by IL-4. IL-4 did not modulate additional arachidonic acid pathway enzymes mPGES-1 and 15-PGDH, which could potentially be responsible for regulating PGE(2) production. Overall, our studies demonstrate that IL-4 has the capacity to inhibit COX-2 mRNA transcription in NSCLC cells and the inhibition of PGE(2) appears to be predominately COX-2 dependent.

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