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John, G. ; Chillappagari, S.* ; Rubin, B.K.* ; Gruenert, D.C.* ; Henke, M.O.*

Reduced surface toll-like receptor-4 expression and absent interferon-γ-inducible protein-10 induction in cystic fibrosis airway cells.

Exp. Lung Res. 37, 319-326 (2011)
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
ABSTRACT As part of the innate and adaptive immune system, airway epithelial cells secrete proinflammatory cytokines after activation of Toll-like receptors (TLRs) by pathogens. Nevertheless, cystic fibrosis (CF) airways are chronically infected with Pseudomonas aeruginosa, suggesting a modified immune response in CF. The authors have shown that in CF bronchial epithelial cells, a reduced surface expression of TLR-4 causes a diminished interleukin (IL)-8 and IL-6 response upon lipopolysaccharide (LPS) stimulation. However, there is no information regarding activation of the MyD88 (myeloid differentiation primary response gene 88)-independent TLR-4 signaling pathway by LPS, which results in the activation of adaptive immune responses by secretion of the T cell-recruiting chemokine interferon-γ-inducible protein (IP)-10. Therefore, the authors investigated the induction of IP-10 in CF bronchial epithelial cell line CFBE41o- and its CFTR-corrected isotype under well-differentiating conditions. TLR-4 surface expression was significantly reduced in CFBE41o- by a factor of 2, compared to the CFTR-corrected cells. In CFTR-corrected cells, stimulation with LPS increased IP-10 secretion. Incubating cells with siRNA directed against TLR-4 inhibited the LPS stimulated increase of IP-10 in CFTR-corrected cells. The reduced TLR-4 surface expression in CF cells causes the loss of induction of IP-10 by LPS. This could compromise adaptive immune responses in CF due to a reduced T-cell recruitment.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter adaptive immunity; airway epithelium; CFTR, IFN-γ–-nducible protein (IP)-10; inflammation; innate immunity; Toll-like receptor
ISSN (print) / ISBN 0190-2148
e-ISSN 1521-0499
Quellenangaben Band: 37, Heft: 6, Seiten: 319-326 Artikelnummer: , Supplement: ,
Verlag Informa Healthcare
Begutachtungsstatus Peer reviewed