Yersinia YopJ inhibits pro-inflammatory molecule expression in human bronchial epithelial cells.
Human bronchial epithelial cell pro-inflammatory molecule expression plays a role in the pathogenesis of airway diseases. We hypothesize that Yersinia outer protein-J (YopJ), a Yersinia virulence effector which inhibits mitogen activated protein (MAP) kinase kinases (MKKs), attenuates epithelial cell pro-inflammatory molecule expression. 16HBE14o-cells were co-transfected with cDNAs encoding Yersinia pseudotuberculosis YopJ or empty vector. Expression of YopJ reduced activation of extracellular signal regulated kinase (ERK)-2, Jun amino terminal kinase (JNK)-1 and IkappaB kinase (IKK)-beta. YopJ also blocked transactivation of NF-kappaB and AP-1 promoter sequences which has been shown to regulate chemokine expression. Finally, expression of YopJ reduced transcription from the IL-8, RANTES (regulated upon activation, normal T cell expressed and secreted) and intercellular adhesion molecule (ICAM)-1 promoters. We conclude that YopJ expression blocks the innate immune response in lung epithelial cells, the site of Yersinia pestis infection. Inhibition of bronchial epithelial cell responses by YopJ is consistent with the notion that MAP kinases regulates bronchial epithelial cell pro-inflammatory molecule expression.
Zhou
Limei
L
Department of Pediatrics, University of Chicago, Chicago, IL 60637-1470, USA.
Tan
Alan
A
Hershenson
Marc B
MB
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001980:Bronchi / Q000166:cytology / Q000276:immunology*; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D007155:Immunologic Factors / Q000235:genetics / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology*; D014162:Transfection; D015007:Yersinia / Q000235:genetics
D001426:Bacterial Proteins; D018946:Chemokine CCL5; D007155:Immunologic Factors; D016209:Interleukin-8; D016328:NF-kappa B; D018808:Transcription Factor AP-1; C109227:YopP protein, Yersinia; D018799:Intercellular Adhesion Molecule-1