Activation of lipid metabolism contributes to interleukin-8 production during Chlamydia trachomatis infection of cervical epithelial cells.

Published

Journal Article

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.

Full Text

Cited Authors

  • Fukuda, EY; Lad, SP; Mikolon, DP; Iacobelli-Martinez, M; Li, E

Published Date

  • July 2005

Published In

Volume / Issue

  • 73 / 7

Start / End Page

  • 4017 - 4024

PubMed ID

  • 15972489

Pubmed Central ID

  • 15972489

Electronic International Standard Serial Number (EISSN)

  • 1098-5522

International Standard Serial Number (ISSN)

  • 0019-9567

Digital Object Identifier (DOI)

  • 10.1128/IAI.73.7.4017-4024.2005

Language

  • eng