LPS enhances TLR4 expression and IFN-γ production via the TLR4/IRAK/NF-κB signaling pathway in rat pulmonary arterial smooth muscle cells

The aim of the present study was to investigate the role of the Toll-like receptor (TLR) 4 signaling pathway in cellular response to lipopolysaccharide (LPS) in rat pulmonary artery smooth muscle cells (PASMCs). Chronic obstructive pulmonary disease (COPD) rats were established with passive inhaling cigarette smoke plus injection of LPS. The TLR4 protein in lung tissues was determined with immunohistochemical staining and protein levels of the components of the TLR4 pathway in PASMCs were analyzed with western blotting. The production of interferon (IFN)-gamma upon LPS stimulation in PASMCs was measured with ELISA. TLR4 expression in lung tissue from COPD rats was increased obviously compared with that in normal group. LPS enhances TLR4 expression in rat PASMCs and induced production of IFN-gamma dramatically. LPS treatment resulted in increased phosphor-interleukin-1 receptor-associated kinase (IRAK), I kappa B and I kappa B kinase, as well as the total protein of nuclear factor (NF)-kappa B p65. TLR4 inhibitor TAK-242, IRAK1/4 inhibitor and NF-kappa B inhibitor Bay 117082 were capable of suppressing the effects of LPS. TLR4 signaling pathway is functional in PASMCs, and may be involved in the inflammatory response during the pathogenesis of COPD.