Cigarette smoke extract-mediated FABP4 upregulation suppresses viability and induces apoptosis, inflammation and oxidative stress of bronchial epithelial cells by activating p38 MAPK/MK2 signaling pathway

Abstract

Background Long-term inhalation of cigarette smoke is considered to be one of the main causes of bronchial epithelioid cell damage, but its underlying mechanism has to be further clarified. Methods Gene expression at mRNA level and protein levels were detected by qRT-PCR and western blot analysis respectively. CCK-8, TUNEL assays, ELISA, western blot analysis and commercial kits were utilized to test cell viability, apoptosis inflammatory response and oxidative stress. The correlation between fatty acid binding protein 4 (FABP4) and the p38 mitogen-activated protein kinase (MAPK)/MAPK activated kinase 2 (MK2) signaling pathway was verified by western blot analysis and rescue assays. Results Cigarette smoke extract (CSE) exposure decreased viability, induced apoptosis and inflammatory response in 16HBE cells. Moreover, the expression of FABP4 in CSE-treated 16HBE cells was up-regulated in a time and dose-dependent manner. Ablation of FABP4 in 16HBE cells significantly protected against CSE-mediated cell viability decline and apoptosis. Further, FABP4 knockdown suppressed inflammatory response by down-regulating the elevated levels of cellular inflammatory factors including TNF-α, IL-1β, IL-6, Cyclooxygenase-2 (Cox-2) and inducible nitric oxide synthase (iNOS) in CSE-treated 16HBE cells. The oxidative stress induced by CSE in 16HBE cells was also inhibited by FABP4 silence as evidence by reduced ROS and MDA level but increased SOD activity caused by FABP4 silence. Finally, all the above effects of FABP4 silence on CSE-treated 16HBE cells were reversed by asiatic acid, an agonist of p38 mitogen-activated protein kinase (MAPK). Conclusions The up-regulation of FABP4 expression mediated by CSE exerted pro-inflammatory, pro-oxidative stress and pro-apoptotic effects on bronchial epithelial cells by activating the p38 MAPK/MK2 signaling pathway. Our findings help to further understand the underlying mechanism of cigarette smoke-induced bronchial inflammation.

Effects of low-dose filtered kretek cigarette smoke on bronchial smooth muscle in male Sprague-Dawley rats

“…(40) More clearly it has been demonstrated that cigarette smoke induces lung inflammation by various mechanisms. (41,42) As a result of exposure to filtered kretek cigarette smoke, specifically the bronchial mucosa undergoes hyperplasia. A previous study demonstrated that exposure to cigarette smoke at a dose of 2 sticks/day for 14 days caused changes in epithelial structure in rat airways.…”

Elevated serum fatty acid-binding protein 4 level predicts all-cause and cardiovascular mortality in peritoneal dialysis patients: a five-year study

“…Vascular calcification in kidney failure rats fed a high-fat diet was aggravated by obesity-related inflammation through activation of the MAPK pathway [ 38 ], and inhibition of p38 MAPK decreased VSMC calcification stimulated by inorganic phosphate [ 39 ]. FABP4 exerts pro-inflammatory, pro-oxidative stress, and pro-apoptotic effects on bronchial epithelial cells by activating the p38 MAPK pathway [ 40 ]. We speculate that FABP4 may upregulate the osteogenic differentiation of VSMCs and deteriorate vascular calcification by activating the MAPK pathways.…”

“…Emerging data have demonstrated that FABP4 may promote the progression of chronic inflam­mation in patients with metabolic syndromes [ 41 ]. The up-regulation of FABP4 exerted a pro-inflammation effect on macrophages [ 42 ] and bronchial epithelial cells [ 40 ]. In contrast, FABP4 inhibitors attenuated inflammation and endoplasmic reticulum stress in the islets of rats with metabolic syndrome [ 41 ].…”

Glycyrrhizic Acid and Compound Probiotics Supplementation Alters the Intestinal Transcriptome and Microbiome of Weaned Piglets Exposed to Deoxynivalenol

“…PLIN1 and PLIN4 are the member of perilipin-family proteins related to lipid droplet (LD) surface proteins, which play vital role during fat metabolism of adipose tissue lipolysis and fat storage in adipocytes [21,22]. Fatty acid binding protein 4 (FABP4), a subtype of fatty acid-binding protein family, is a key transmitter of lipid metabolism and inflammatory reaction [23]. ADIPOQ, also known as adiponectin and mainly expressed in adipose tissue, is associated with lipid metabolism and hormone production, including fatty acid uptake, binding, transport, oxidation, and lipoprotein assembly [24].…”