Open AccessTranscription factor complex AP ‐1 mediates inflammation initiated by C hlamydia pneumoniae infection
Author(s) -
Wang Anyou,
AlKuhlani Mufadhal,
Johnston S. Claiborne,
Ojcius David M.,
Chou Joyce,
Dean Deborah
Publication year - 2013
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/cmi.12071
Subject(s) - biology , chlamydiae , chlamydophila pneumoniae , inflammation , immunology , tlr2 , tlr3 , innate immune system , junb , interleukin 8 , tumor necrosis factor alpha , tlr4 , immune system , toll like receptor , transcription factor , chlamydia , chlamydiaceae , gene , biochemistry
Summary C hlamydia 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, IL 8, CD 38 and tumour necrosis factor compared with controls. These mediators have been shown to be associated with C . pneumoniae disease. Expression of AP ‐1 components wasregulated by MAPK 3 K 8, a MAPK pathway component. Additionally, knock‐down of JUN and FOS showed significantly decreased expression of T oll‐like receptor ( TLR )3 during infection, implicating JUN and FOS in TLR 3 regulation. TLR 3 stimulation led to elevated IL 8. These findings suggest that C . pneumoniae initiates signalling via TLR 3 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.