Activation of the host cell proinflammatory interleukin-8 response by Chlamydia trachomatis.
Diseases associated with Chlamydia are caused by inflammation-associated tissue damage following repeated or chronic infection; however, the mechanism by which the inflammatory response is induced is unknown. The inflammatory cytokine interleukin-8 (IL-8) is produced by C. trachomatis-infected epithelial cells in a bacterial growth-dependent manner. We hypothesized that IL-8 is induced through activation of host signalling pathways within Chlamydia-infected cells. Bacterial protein synthesis occurring after 15 h post infection (hpi) was required for the induction of IL-8, thus, increases in IL-8 mRNA are due to chlamydial growth or a bacterial product produced at 15 hpi. The induction of IL-8 was not dependent on soluble factors in the supernatant of C. trachomatis-infected cells and therefore was associated with an internal cellular signal. The AP-1, NFIL6 (C/EBPbeta) and NFkappaB transcriptional regulatory sites of the IL-8 promoter and the host NFkappaB signalling pathway were necessary for IL-8 induction by C. trachomatis. We conclude that a C. trachomatis growth-dependent factor produced at mid-developmental stage induces IL-8 within the epithelial cell it infects through activation of host signalling pathways.
Buchholz
Kerry R
KR
Program in Infectious Diseases and Immunity, University of California, Berkeley, CA 94720, USA.
Stephens
Richard S
RS
D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D002692:Chlamydia trachomatis / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D006367:HeLa Cells; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D008957:Models, Genetic; D016328:NF-kappa B / Q000378:metabolism; D016133:Polymerase Chain Reaction / Q000379:methods; D014176:Protein Biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism
D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D012333:RNA, Messenger; D018808:Transcription Factor AP-1