Elevated CXCL14 in Induced Sputum Was Associated with Eosinophilic Inflammation and Airway Obstruction in Patients with Asthma

Int Arch Allergy Immunol. 2022;183(11):1216-1225. doi: 10.1159/000526367. Epub 2022 Sep 5.

Abstract

Introduction: CXCL14 involved in inflammatory processes was upregulated in the asthma expression profile datasets in our pilot study. However, the expression of CXCL14 in induced sputum and its potential clinical role in asthma were poorly reported.

Objective: We sought to detect CXCL14 expression in airway epithelium and induced sputum cells of asthma and explore its potential clinical implications.

Methods: The expression of CXCL14 in asthma was analyzed using R software based on multiple microarray datasets, including GSE43696, GSE63142, GSE67940, and GSE76262. Subsequent verification of the CXCL14 expression pattern in induced sputum and bronchial epithelium cells was performed by qRT-PCR and ELISA. Besides, the correlations between CXCL14 and eosinophilic inflammation indicators (FeNO, EOS#, and IgE), Th2 signature genes (SERPINB2, POSTN, and CLCA1), inflammatory cytokines (IL-4, IL-5, IL-10, IL-13, IL-25, IL-33, TSLP, IL-8, IL-17A, IFN-γ, and IL-2), and airway obstruction indicators (pulmonary function and mucin secretion) were further explored.

Results: The expression of CXCL14 in epithelium and sputum cells was upregulated in asthma and positively correlated with clinical eosinophilic indicators. The protein levels of CXCL14 were positively associated with Th2 signature genes (SERPINB2, POSTN, and CLCA1) and Th2 cytokines (IL-4, IL-5, IL-10, IL-13, IL-25, IL-33, and TSLP). Increased expression of CXCL14 was also observed in BEAS-2B cells stimulated by the cytokine IL-4. Furthermore, the expression of CXCL14 was positively correlated with MUC5AC secretion and negatively associated with pulmonary function.

Conclusions: Upregulated CXCL14 in asthma was positively correlated with inflammatory indicators and negatively correlated with pulmonary function, which indicated that upregulated CXCL14 might act as a pathogenic gene through involvement in Th2 inflammation in asthma.

Keywords: Asthma; CXCL14; Eosinophilic inflammation; Induced sputum; Th2 cytokines.

MeSH terms

  • Airway Obstruction* / metabolism
  • Asthma* / metabolism
  • Chemokines, CXC / metabolism
  • Cytokines / metabolism
  • Eosinophilia* / metabolism
  • Humans
  • Inflammation / genetics
  • Inflammation / metabolism
  • Interleukin-10 / metabolism
  • Interleukin-13 / metabolism
  • Interleukin-33 / metabolism
  • Interleukin-4 / metabolism
  • Interleukin-5
  • Pilot Projects
  • Sputum

Substances

  • Interleukin-13
  • Interleukin-33
  • Interleukin-10
  • Interleukin-5
  • Interleukin-4
  • Cytokines
  • CXCL14 protein, human
  • Chemokines, CXC