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COX-2 inhibition enhances the TH2 immune response to epicutaneous sensitization


, : COX-2 inhibition enhances the TH2 immune response to epicutaneous sensitization. Journal of Allergy and Clinical Immunology 116(2): 390-396

Background: Mechanical injury to the skin by scratching is an important feature of atopic dermatitis (AD). Objective: To investigate the role of COX-2 in allergic skin inflammation elicited by epicutaneous (EC) sensitization via introduction of ovalbumin through shaved tape-stripped skin.Methods: COX-2 mRNA was measured by quantitative PCR, and COX-2 protein was measured by Western blotting. We investigated the effect of administration of the COX-2 selective inhibitor NS-398 during EC sensitization with ovalbumin in a mouse model of AD characterized by eosinophil skin infiltration, elevated total and antigen specific IgE, and a systemic T(H)2 response to antigen. We further examined the response of COX-2-deficient mice to EC immunization with ovalbumin.Results: Tape stripping caused a transient increase in skin COX-2 mRNA. In contrast, COX-2 mRNA was not increased after ovalbumin sensitization. Infiltration by eosinophils and expression of IL-4 mRNA in ovalbumin-sensitized skin sites, ovalbumin specific IgE and IgG(1) antibody responses, and IL-4 secretion by splenocytes after ovalbumin stimulation were all significantly increased in EC mice that received NS-398. In contrast, ovalbumin specific IgG(2a). antibody response and IFN-gamma secretion by splenocytes after ovalbumin stimulation were significantly decreased in these mice. COX-2-deficient mice also exhibited an enhanced systemic TH2 response to EC sensitization.Conclusion: These results demonstrate that COX-2 limits the TH2 response to EC sensitization and suggest that COX inhibitors may worse. allergic skin inflammation in patients with AD.

US$19.90

PMID: 16083795

DOI: 10.1016/j.jaci.2005.03.042


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