Department of Biology, University of North Carolina at Charlotte, Charlotte, NC 28223
Production of IL-12 and IFN-γ secretion are important components of the protective host response against the intracellular bacterial pathogen, Salmonella typhimurium. While infection with Salmonella does elicit this T helper type 1 response, its magnitude does not appear to be sufficient to prevent infection or limit pathogenesis. Therefore we have investigated factors which might limit a T helper type 1 response following infection. Previously we found that infection of antigen presenting cells with Salmonella dramatically increases cyclooxygenase-2 (COX-2) activity, resulting in high levels of prostaglandin E2 (PGE2). Since PGE2 production can have profound effects on initiation of T helper type 1 responses, we questioned whether this mediator might limit antigen-specific T cell activation. Here we show that blockage of COX-2 activity with the selective inhibitor celecoxib leads to enhancement of the T helper type 1 components stimulated by Salmonella infection. In vitro studies demonstrate the induction of IL-12 and IFN-γ upon Salmonella exposure, which are further increased following COX-2 inhibition. Taken together these in vitro studies suggest that COX-2 activity can limit a salmonella-initiated T helper type 1 response.
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* Address correspondence to this author at the Department of Biology, University of North Carolina at Charlotte, 9201 University City Blvd., Charlotte, N.C. 28223; Tel: (704) 687-8677; Fax: (704) 687-3128; E-mail: KLPOST@UNCC.EDU