FGF2 is overexpressed in asthma and promotes airway inflammation through the FGFR/MAPK/NF-κB pathway in airway epithelial cells

Abstract

Background Airway inflammation is the core pathological process of asthma, with the key inflammatory regulators incompletely defined. Recently, fibroblast growth factor 2 (FGF2) has been reported to be an inflammatory regulator; however, its role in asthma remains elusive. This study aimed to investigate the immunomodulatory role of FGF2 in asthma. Methods First, FGF2 expression was characterised in clinical asthma samples and the house dust mite (HDM)-induced mouse chronic asthma model. Second, recombinant mouse FGF2 (rm-FGF2) protein was intranasally delivered to determine the effect of FGF2 on airway inflammatory cell infiltration. Third, human airway epithelium-derived A549 cells were stimulated with either HDM or recombinant human interleukin-1β (IL-1β) protein combined with or without recombinant human FGF2. IL-1β-induced IL-6 or IL-8 release levels were determined using enzyme-linked immunosorbent assay, and the involved signalling transduction was explored via Western blotting. Results Compared with the control groups, the FGF2 protein levels were significantly upregulated in the bronchial epithelium and alveolar areas of clinical asthma samples (6.70 ± 1.79 vs. 16.32 ± 2.40, P = 0.0184; 11.20 ± 2.11 vs. 21.00 ± 3.00, P = 0.033, respectively) and HDM-induced asthmatic mouse lung lysates (1.00 ± 0.15 vs. 5.14 ± 0.42, P < 0.001). Moreover, FGF2 protein abundance was positively correlated with serum total and anti-HDM IgE levels in the HDM-induced chronic asthma model (R2 = 0.857 and 0.783, P = 0.0008 and 0.0043, respectively). Elevated FGF2 protein was mainly expressed in asthmatic bronchial epithelium and alveolar areas and partly co-localised with infiltrated inflammatory cell populations in HDM-induced asthmatic mice. More importantly, intranasal instillation of rm-FGF2 aggravated airway inflammatory cell infiltration (2.45 ± 0.09 vs. 2.88 ± 0.14, P = 0.0288) and recruited more subepithelial neutrophils after HDM challenge [(110.20 ± 29.43) cells/mm2 vs. (238.10 ± 42.77) cells/mm2, P = 0.0392] without affecting serum IgE levels and Th2 cytokine transcription. In A549 cells, FGF2 was upregulated through HDM stimulation and promoted IL-1β-induced IL-6 or IL-8 release levels (up to 1.41 ± 0.12- or 1.44 ± 0.14-fold change vs. IL-1β alone groups, P = 0.001 or 0.0344, respectively). The pro-inflammatory effect of FGF2 is likely mediated through the fibroblast growth factor receptor (FGFR)/mitogen-activated protein kinase (MAPK)/nuclear factor kappa B (NF-κB) pathway. Conclusion Our findings suggest that FGF2 is a potential inflammatory modulator in asthma, which can be induced by HDM and acts through the FGFR/MAPK/NF-κB pathway in the airway epithelial cells.

Microglia Autophagy Mediated by TMEM166 Promotes Ischemic Stroke Secondary to Carotid Artery Stenosis

“…Abnormal migration and proliferation of vascular smooth muscle cells (VSMCs) are key triggers of atherosclerosis and stenosis [ 23 ]. Inflammation has been shown to contribute to the abnormal migration of VSMCs and the formation of atherosclerotic plaques [ 24 - 27 ], and autophagy has a close association with inflammation [ 28 ]. In this study, TMEM166 expression was detected in the inner part of the sclerotic plaque, and the expression was significantly higher than in other segments of the plaque, accompanied by a large amount of enrichment of inflammatory mediators.…”

Clinical Efficacy of Ulinastatin Combined with Azithromycin in the Treatment of Severe Pneumonia in Children and the Effects on Inflammatory Cytokines and Oxidative Stress: A Retrospective Cohort Study

“…Compared to AZM alone, the combination of UTI and AZM resulted in a notable reduction in the levels of inflammatory cytokines, including TNF-α, IL-6, IL-10, and IL-1β. Previous studies [36][37][38][39][40] have indicated that these inflammatory cytokines are typically produced through the NF-κB/MAPKs/JNK signaling pathways. It has been reported that UTI can attenuate the release of inflammatory cytokines by inhibiting the phosphorylation of p65 in the NF-κB signaling pathway, as well as inhibiting the phosphorylation of ERK and JNK within the MAPKs family.…”

Protective Effects of Platycodin D3 on Airway Remodeling and Inflammation via Modulating MAPK/NF-κB Signaling Pathway in Asthma Mice

“…In addition, studies have found that MAPK/NF- κ B signaling acted as an inflammatory promoter and could control asthmatic airway responses via regulating the MAPK/NF- κ B pathway [ 30 , 31 ], as well as inhibit lung inflammation in asthmatic mice [ 32 ]. Previous studies had found that airway remodeling could be improved through regulating the MAPK/NF- κ B pathway [ 33 , 34 ].…”