Role of TLR4/NF-κB signalling pathway in pulmonary arterial hypertension in patients with chronic obstructive pulmonary disease

Objective: 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). Study Design: An experimental study. Place and Duration of Study: Department of Respiratory Disease, The Hospital Affiliated to Jiangnan University, Wuxi, Jiangsu, China, from June 2018 to December 2019. Methodology: 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 blood mononuclear cells (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. Results: 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 and p=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 between IL-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). Conclusions: 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. (author)