title: Secretion of proinflammatory cytokines by epithelial cells in response to Chlamydia infection suggests a central role for epithelial cells in chlamydial pathogenesis.
abstract: Chlamydia species infect epithelial cells at mucosal surfaces, and are major causes of sexually transmitted diseases. Infection is characterized by inflammation which is exacerbated upon reinfection, ultimately leading to tissue damage and scarring. Although central for the development of disease manifestations, little is known about the mechanisms that initiate and sustain the inflammatory response to Chlamydia. Infection of cervical and colonic epithelial cells with Chlamydia trachomatis and Chlamydia psittaci is shown in the present studies to upregulate mRNA expression and secretion of the proinflammatory cytokines IL-8, GRO alpha, GM-CSF, and IL-6. In contrast to the rapid, but transient, cytokine induction following infection with other invasive bacteria, the epithelial cytokine response to Chlamydia was delayed until 20-24 h after infection, persisted throughout the chlamydial growth cycle (2-4 d), and required bacterial protein synthesis. Moreover, epithelial cell lines and primary endocervical epithelial cells released IL-1alpha after Chlamydia infection, and increased secretion of the proinflammatory cytokines could be inhibited by anti-IL-1alpha. This suggests that IL-1alpha, released following lysis of infected epithelial cells, may amplify the inflammatory response by stimulating additional cytokine production by noninfected neighboring cells. These findings suggest a novel pathophysiologic concept wherein the acute host response to Chlamydia at mucosal surfaces is primarily initiated and sustained by epithelial cells, the first and major targets of chlamydial infection.
authors.affiliation: Francis I. Proctor Foundation, University of California, San Francisco 94143, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Rasmussen
authors.forename: L
authors.initials: L
authors.lastname: Eckmann
authors.forename: A J
authors.initials: AJ
authors.lastname: Quayle
authors.forename: L
authors.initials: L
authors.lastname: Shen
authors.forename: Y X
authors.initials: YX
authors.lastname: Zhang
authors.forename: D J
authors.initials: DJ
authors.lastname: Anderson
authors.forename: J
authors.initials: J
authors.lastname: Fierer
authors.forename: R S
authors.initials: RS
authors.lastname: Stephens
authors.forename: M F
authors.initials: MF
authors.lastname: Kagnoff
mesh_terms: D000199:Actins / Q000032:analysis; D001426:Bacterial Proteins / Q000096:biosynthesis; D002478:Cells, Cultured; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000378:metabolism; D002690:Chlamydia Infections / Q000276:immunology*; D002692:Chlamydia trachomatis / Q000472:pathogenicity*; D002691:Chlamydophila psittaci / Q000472:pathogenicity*; D004847:Epithelial Cells; D004848:Epithelium / Q000276:immunology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D018928:Immunity, Mucosal; D007249:Inflammation / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1 / Q000378:metabolism* / Q000502:physiology*; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011135:Polysaccharides, Bacterial / Q000009:adverse effects; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000032:analysis
chemical_list: D000199:Actins; D001426:Bacterial Proteins; C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D011135:Polysaccharides, Bacterial; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D016178:Granulocyte-Macrophage Colony-Stimulating Factor