title: Transcription factor complex AP-1 mediates inflammation initiated by Chlamydia pneumoniae infection.
abstract: Chlamydia pneumoniae is responsible for a high prevalence of respiratory infections worldwide and has been implicated in atherosclerosis. Inflammation is regulated by transcription factor (TF) networks. Yet, the core TF network triggered by chlamydiae remains largely unknown. Primary human coronary artery endothelial cells were mock-infected or infected with C. pneumoniae to generate human transcriptome data throughout the chlamydial developmental cycle. Using systems network analysis, the predominant TF network involved receptor, binding and adhesion and immune response complexes. Cells transfected with interfering RNA against activator protein-1 (AP-1) members FOS, FOSB, JUN and JUNB had significantly decreased expression and protein levels of inflammatory mediators interleukin (IL)6, IL8, CD38 and tumour necrosis factor compared with controls. These mediators have been shown to be associated with C. pneumoniae disease. Expression of AP-1 components was regulated by MAPK3K8, a MAPK pathway component. Additionally, knock-down of JUN and FOS showed significantly decreased expression of Toll-like receptor (TLR)3 during infection, implicating JUN and FOS in TLR3 regulation. TLR3 stimulation led to elevated IL8. These findings suggest that C. pneumoniae initiates signalling via TLR3 and MAPK that activate AP-1, a known immune activator in other bacteria not previously shown for chlamydiae, triggering inflammation linked to C. pneumoniae disease.
authors.affiliation: Center for Immunobiology and Vaccine Development, Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA.
authors.forename: Anyou
authors.initials: A
authors.lastname: Wang
authors.forename: Mufadhal
authors.initials: M
authors.lastname: Al-Kuhlani
authors.forename: S Claiborne
authors.initials: SC
authors.lastname: Johnston
authors.forename: David M
authors.initials: DM
authors.lastname: Ojcius
authors.forename: Joyce
authors.initials: J
authors.lastname: Chou
authors.forename: Deborah
authors.initials: D
authors.lastname: Dean
mesh_terms: D050197:Atherosclerosis / Q000378:metabolism* / Q000382:microbiology / Q000503:physiopathology; D016993:Chlamydophila pneumoniae / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D003331:Coronary Vessels / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D042783:Endothelial Cells; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism; D018410:Pneumonia, Bacterial / Q000378:metabolism / Q000382:microbiology / Q000503:physiopathology; D051196:Toll-Like Receptor 3 / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D018808:Transcription Factor AP-1