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

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

  • Mil Med Res. 2022 Jan 29;9(1):7. doi: 10.1186/s40779-022-00366-3.
Yuan-Yang Tan  # 1 Hui-Qin Zhou  # 1 Yu-Jing Lin  # 2 Liu-Tong Yi  # 2 Zhuang-Gui Chen 3 Qing-Dong Cao 4 Yan-Rong Guo 1 Zhao-Ni Wang 1 Shou-Deng Chen 1 Yang Li 1 De-Yun Wang 5 Yong-Kang Qiao 6 Yan Yan 7 8
Affiliations

Affiliations

  • 1 Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, 519000, Guangdong, China.
  • 2 Department of Pathology, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, 519000, Guangdong, China.
  • 3 Department of Pediatrics, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630, China.
  • 4 Department of Cardiothoracic Surgery, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, 519000, Guangdong, China.
  • 5 Department of Otolaryngology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore, 119228, Singapore.
  • 6 BGI-Shenzhen, Shenzhen, 518083, Guangdong, China. qiaoyongkang@genomics.cn.
  • 7 Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, 519000, Guangdong, China. yanyan35@mail.sysu.edu.cn.
  • 8 Central Laboratory, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, 519000, Guangdong, China. yanyan35@mail.sysu.edu.cn.
  • # Contributed equally.
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.

Keywords

Airway epithelial cell; Airway inflammation; Asthma; Fibroblast growth factor 2 (FGF2); House dust mite chronic model.

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