Expression profiles of Toll-like receptors in non-small cell lung cancer and idiopathic pulmonary fibrosis.Int J Oncol. 2012 May; 40(5):1397-404.IJ
Patients with idiopathic pulmonary fibrosis (IPF) have a higher incidence of lung cancer. The role of Toll-like receptors (TLRs), a key component of the innate immunity, in interstitial lung diseases (ILDs) and lung cancer pathogenesis is not clarified. TLR2, TLR3, TLR4, TLR7, TLR8 and TLR9 mRNA expression was quantitatively measured by real-time reverse transcriptase polymerase chain reaction (RT-PCR) in bronchoalveolar lavage fluid (BALF) of 16 IPF patients, 16 non-small cell lung cancer (NSCLC) patients and 9 control subjects. TLR2, TLR3, TLR4 and TLR9 protein expression was assessed on BALF T-lymphocytes using flow cytometry. TLR3 mRNA expression was significantly higher in NSCLC compared to IPF (p=0.023) and controls (p=0.001). TLR7 mRNA expression levels were significantly higher in both NSCLC and IPF groups compared to controls (p=0.029, p=0.009). TLR9 expression at the mRNA level was significantly higher in both NSCLC and IPF groups compared to controls (p=0.01, p=0.001). Finally, TLR2 mRNA expression was significantly higher in IPF patients compared to controls (p=0.042). Flow cytometry revealed decreased TLR3 and TLR9 expression in IPF patients compared to the NSCLC group (p=0.02, p=0.014) and decreased TLR9 expression in IPF compared with the controls (p=0.04). TLR2 protein expression was significantly higher in IPF patients compared to NSCLC (p=0.04). Increased expression of endosomal TLRs in NSCLC patients and elevated expression of TLR2 in pulmonary fibrosis are the main results of this study. These results do not provide support for a common TLR pathway hypothesis between NSCLC and IPF.