Blocking tumor necrosis factor-α delays progression of chronic obstructive pulmonary disease in rats through inhibiting MAPK signaling pathway and activating SOCS3/TRAF1

Abstract

The present study was conducted in order to study the detailed molecular mechanism of tumor necrosis factor (TNF)-α in chronic obstructive pulmonary disease (COPD). The rats were treated with cigarette smoke (CS) and lipopolysaccharide (LPS) to establish the COPD model. Next, the changes in lung injury in COPD rats with TNF-α knockdown was tested. Meanwhile, the regulation of TNF-α on MAPK pathway and its downstream molecules (SOCS3/TRAF1) was determined by western blotting. On this basis, the activation of MAPK and inhibition of SOCS3/TRAF1 was also examined. Subsequently, the lung function was tested with the plethysmograph, the cells of bronchoalveolar lavage fluid was counted and classified. Furthermore, lung tissue sections were stained with hematoxylin and eosin to verify whether the treatment of MAPK pathway and downstream molecules affected the effect of TNF-α knockdown on COPD. The present study showed that TNF-α knockdown could alleviate the decrease in the function and inflammatory injury of the lungs of rats with COPD. Western blot analysis verified that TNF-α knockdown could inhibit the activation of MAPK pathway and increase the expression of SOCS3/TRAF1. The following experimental results showed that the relief of lung injury caused by TNF-α knockdown could be deteriorated by activating MAPK pathway. It was also found that the symptom of COPD was decreased following transfection with sh-TNF-α but worsened by SOCS3/TRAF1 knockdown. Overall, TNF-α knockdown inhibited the activation of MAPK pathway and increased the expression of SOCS3/TRAF1, thus delaying the process of COPD.

Melatonin and mesenchymal stem cells co-administration alleviates chronic obstructive pulmonary disease via modulation of angiogenesis at the vascular-alveolar unit

“…In addition, accompanied emphysematous changes due to parenchymal destruction with reduced ability for gas exchange and refractory asthma might have a share in the expiratory functional deterioration [ 10 , 47 ]. Previous studies were also in support of our study indicating airflow limitation mainly during the expiration demonstrated the same results showing that the expiratory lung function indices were affected in the COPD group [ 19 , 55 , 79 , 82 ]. However, Xiao et al [ 82 ] showed significant changes in inspiratory parameters as well, but they used different methods of induction and measurement techniques so as they induced COPD using cigarette smoking only for 28 weeks and stated that the inspiratory changes occurred after 14 weeks.…”

scRNA-seq and scATAC-seq analyses highlight the role of TNF signaling in chronic obstructive pulmonary disease progression

“…COPD patients have previously been shown to exhibit elevated pulmonary TNF-α concentrations as compared to healthy individuals, and TNF-α has been linked to COPD progression [51] . Overexpression of TNF-α can lead to emphysema, pulmonary brosis, and muscle mass reduction in COPD patients [52] . Individuals with COPD exhibit characteristic in ammation that affects the airways, pulmonary vasculature, and parenchyma such that higher numbers of T cells and macrophages are present within the lungs.…”