Role of TLR4/NF-κB Signalling Pathway in Pulmonary Arterial Hypertension in Patients with Chronic Obstructive Pulmonary Disease.

Abstract

To determine the role of toll-like receptor 4 (TLR4)/ nuclear factor kappa B (NF-κB) signalling pathway in pulmonary arterial hypertension (PAH) in patients with chronic obstructive pulmonary disease (COPD). An experimental study. Department of Respiratory Disease, The Hospital Affiliated to Jiangnan University, Wuxi, Jiangsu, China, from June 2018 to December 2019. Subjects included 98 COPD patients and 22 healthy individuals (control group). COPD patients were divided into two groups as PAH group (PAH group, n=57) and normal pulmonary arterial pressure group (nPAP group, n=41). TLR4 and NF-κB in peripheral bloodmononuclearcells (PBMC)were measured by real-time polymerase chain reaction (RT-PCR); and inflammatory cytokine of IL-6 and TNF-α were estimated by enzyme-linked immunosorbent assay (ELISA) of three groups. The levels of TLR4, NF-κB and inflammatory cytokine of IL-6 and TNF-α of PAH group were higher than those in nPAP group and controls (all p<0.05); and controls had a lower levels of TLR4, NF-κB and TNF-α than those n PAP group patients (all p<0.05) except for PAP and IL-6 (p=0.121 andp=0.304, respectively). The expression levels of TLR4 and NF-κB in PBMC were positively related to that PAP and inflammatory cytokine of IL-6 and TNF-α in PAH patients with COPD (all p<0.05), but the positive correlation betweenIL-6 and TNF-α expression level was not established (p=0.170). All parameters in the nPAP group had no significant correlation to each other, it is the same in control (all p>0.05). Inflammatory mechanisms play an important role in the development of PAH in patients with COPD. TLR4/NF-κB signal transduction pathway is involved in the pathogenesis of PAH, and the expression levels of TLR4/NF-κB may reflect the severity of PAH in patients with COPD. Key Words: Toll-like receptor 4, Nuclear factor kappa B, Pulmonary arterial hypertension, Chronic obstructive pulmonary disease, Inflammatory cytokine.