Activation of human bronchial epithelial cells by inflammatory cytokines IL-27 and TNF-alpha: implications for immunopathophysiology of airway inflammation.

Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
Journal of Cellular Physiology (Impact Factor: 4.22). 03/2010; 223(3):788-97. DOI: 10.1002/jcp.22094
Source: PubMed

ABSTRACT Interleukin (IL)-27 is a member of IL-6/IL-12 family cytokines produced by antigen-presenting cells in immune responses. IL-27 can drive the commitment of naive T cells to a T helper type 1 (Th1) phenotype and inhibit inflammation in later phases of infection. Human bronchial epithelial cells have been shown to express IL-27 receptor complex. In this study, we investigated the in vitro effects of IL-27, alone or in combination with inflammatory cytokine tumor necrosis factor (TNF)-alpha on the pro-inflammatory activation of human primary bronchial epithelial cells and the underlying intracellular signaling mechanisms. IL-27 was found to enhance intercellular adhesion molecule 1 (ICAM-1) expression on the surface of human bronchial epithelial cells, and a synergistic effect was observed in the combined treatment of IL-27 and TNF-alpha on the expression of ICAM-1. Although IL-27 did not alter the basal IL-6 secretion from bronchial epithelial cells, it could significantly augment TNF-alpha-induced IL-6 release. These synergistic effects on the up-regulation of ICAM-1 and IL-6 were partially due to the elevated expression of TNF-alpha receptor (p55TNFR) induced by IL-27. Further investigations showed that the elevation of ICAM-1 and IL-6 in human bronchial epithelial cells stimulated by IL-27 and TNF-alpha was differentially regulated by phosphatidylinositol 3-OH kinase (PI3K)-Akt, p38 mitogen-activated protein kinase, and nuclear factor-kappaB pathways. Our results therefore provide a new insight into the molecular mechanisms involved in airway inflammation.

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