The extracellular signal-regulated kinase/mitogen-activated protein kinase pathway induces the inflammatory factor interleukin-8 following Chlamydia trachomatis infection.
Diseases associated with Chlamydia infection, such as pelvic inflammatory disease and ectopic pregnancy, are due to inflammation-mediated tissue damage and scarring that occur after chronic or repeated infections. The inflammatory chemokine interleukin-8 (IL-8) is produced by Chlamydia-infected cells through an endogenous mechanism of activation, independent of soluble factors in the supernatant. The host signaling pathways necessary for this response are not understood, but the mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase (ERK) has been shown to be activated at similar times as IL-8 mRNA up-regulation. The purpose of this study was to elucidate the MAPK pathways necessary to induce the endogenous IL-8 response to Chlamydia trachomatis infection of epithelial cells. IL-8 induced by infection with C. trachomatis L2 was shown to be dependent on ERK and independent of p38 and Jun N-terminal MAPK by use of chemical inhibitors of the signaling pathways. Persistent ERK activation during IL-8 mRNA production at 24 h postinfection was necessary to maintain the response. C. trachomatis serovar D also induced IL-8 in an ERK-dependent manner. We concluded that IL-8 induced during infection of epithelial cells is dependent on continual activation of ERK by C. trachomatis.
Buchholz
Kerry R
KR
Program in Infectious Diseases and Immunity, School of Public Health, University of California-Berkeley, Berkeley, CA 94720, USA.
Stephens
Richard S
RS
D000818:Animals; D002460:Cell Line; D002690:Chlamydia Infections / Q000201:enzymology* / Q000276:immunology / Q000382:microbiology; D002692:Chlamydia trachomatis / Q000254:growth & development / Q000276:immunology* / Q000378:metabolism; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis / Q000276:immunology*; D020935:MAP Kinase Signaling System / Q000276:immunology*; D051379:Mice
D016209:Interleukin-8; D048049:Extracellular Signal-Regulated MAP Kinases