Erythromycin inhibits cigarette smoke-induced inflammation through regulating the PPARγ/NF-κB signaling pathway in macrophages

• Published in: International immunopharmacology Vol. 96; p. 107775
• Main Authors: Qiu, Ju-Feng, Ma, Nan, He, Zhi-Yi, Zhong, Xiao-Ning, Zhang, Jian-Quan, Bai, Jing, Deng, Jing-Min, Tang, Xiao-Juan, Luo, Zhou-Ling, Huang, Mei, Liang, Quan, Wei, Yan-Ling, Tang, Ming-Jiao, Li, Mei-Hua
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.07.2021; Elsevier BV
• Subjects: Cell growth; Cell proliferation; Chronic obstructive pulmonary disease; Chronic obstructive pulmonary disease (COPD); Cigarette smoke; Cigarettes; Erythromycin; Erythromycin (EM); Immunoprecipitation; Inflammation; Inflammatory; Inflammatory response; Interleukin 6; Interleukin 8; Lung diseases; Macrophages; NF-κB; NF-κB protein; Obstructive lung disease; Oxidative stress; Peroxisome proliferator activated receptors γ (PPARγ); Peroxisome proliferator-activated receptors; Reactive oxygen species; Signal transduction; Signaling; Smoke; Tobacco smoke; Inflammatory; Chronic obstructive pulmonary disease (COPD); Oxidative stress; NF-κB; Peroxisome proliferator activated receptors γ (PPARγ); Erythromycin (EM)
• ISSN: 1567-5769; 1878-1705; 1878-1705
• DOI: 10.1016/j.intimp.2021.107775

[Display omitted] •We investigated the anti-inflammatory effects of erythromycin through the PPARγ/NF-κB axis.•The study suggested that PPARγ may be a potential target for COPD prevention. Chronic obstructive pulmonary disease is characterized by chronic inflammation of the airway and lungs. Accumulating evidence has suggested that erythromycin (EM) plays a protective role against cigarette smoke-induced oxidative stress and the inflammatory response. However, the underlying mechanisms remain relatively unclear. The present study aimed to investigate the role of EM in inhibiting cigarette smoke-induced inflammation in human macrophages and its potential mechanism. A Cell Counting Kit-8 assay was used to determine the optimum concentration of EM and cigarette smoke extract (CSE) and it was found that 0.1 and 1% CSE and 0.1, 1.0 and 10 μg/ml EM exerted no significant effect on the cell proliferation activity, whereas 2 and 3% CSE exerted a significant inhibitory effect over the cell proliferation activity. We observed that 10 μmol/ml GW9662 (A PPARγ antagonist) and the presence of 1% CSE could promote the expression and activation of NF-κB p65. And this increased the expression of IL-6, IL-8 and reactive oxygen species (ROS). At the same time, 10 μmol/ml GW9662 and 1% CSE was found to inhibit the expression and activation of peroxisome proliferator activated receptors γ (PPARγ); However, 1 μg/ml EM was discovered to reverse these effects. Co-immunoprecipitation subsequently discovered an interaction between PPARγ and NF-κB p65. In conclusion, the present study suggested that EM may reduce the damage of PPARγ by inhibiting oxidative stress and reducing the expression of ROS and finally relieving cigarette smoke-induced inflammation through the PPARγ/NF-κB signaling pathway in macrophages.