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Infection and Immunity, July 2005, p. 4017-4024, Vol. 73, No. 7
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.7.4017-4024.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Activation of Lipid Metabolism Contributes to Interleukin-8 Production during Chlamydia trachomatis Infection of Cervical Epithelial Cells

Department of Immunology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037

Received 28 October 2004/ Returned for modification 5 January 2005/ Accepted 1 March 2005

Chlamydia trachomatis infection is the most common cause of bacterial sexually transmitted diseases. Infection of the urogenital tract by C. trachomatis causes chronic inflammation and related clinical complications. Unlike other invasive bacteria that induce a rapid cytokine/chemokine production, chlamydial infection induces delayed inflammatory response and proinflammatory chemokine production that is dependent on bacterial growth. We present data here to show that the lipid metabolism required for chlamydial growth contributes to Chlamydia-induced proinflammatory chemokine production. By gene microarray profiling, validated with biochemical studies, we found that C. trachomatis LGV2 selectively upregulated PTGS2 (COX2) and PTGER4 (EP4) in cervical epithelial HeLa 229 cells. COX2 is an enzyme that catalyzes the rate-limiting step of arachidonic acid conversion to prostaglandins, including prostaglandin E2 (PGE2) and other eicosanoids, whereas EP4 is a subtype of cell surface receptors for PGE2. We show that Chlamydia infection induced COX2 protein expression in both epithelial cells and peripheral blood mononuclear cells and promoted PGE2 release. Exogenous PGE2 was able to induce interleukin-8 release in HeLa 229 epithelial cells. Finally, we demonstrated that interleukin-8 induction by Chlamydia infection or PGE2 treatment was dependent on extracellular signal-regulated kinase/mitogen-activated protein activity. Together, these data demonstrate that the host lipid remodeling process required for chlamydial growth contributes to proinflammatory chemokine production. This study also highlights the importance of maintaining a balanced habitat for parasitic pathogens as obligate intracellular organisms.

This is manuscript number 16989-IMM of The Scripps Research Institute.

Editor: D. L. Burns

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