Interleukin-19 upregulates fibronectin and collagen I expression via the NF-κB-Smad2/3 pathway in fibroblasts of patients with chronic rhinosinusitis

Inflamm Res. 2023 Jan;72(1):43-55. doi: 10.1007/s00011-022-01634-7. Epub 2022 Nov 1.

Abstract

Background: Tissue remodeling is a prominent characteristic of chronic rhinosinusitis (CRS). Excess deposition of fibronectin (FN) and collagen (Col) I by fibroblasts is crucial for the pathologic tissue remodeling in CRS without nasal polyps (CRSsNP). Increased interleukin (IL)-19 level in patients with CRS had been demonstrated in our previous studies. Here, we aimed to evaluate the role of IL-19 in mediating FN and Col I expression in CRS.

Methods: Nasal mucosal tissue samples were collected from patients with CRS with nasal polyps (CRSwNP), CRSsNP, and controls. The expression of IL-19, vimentin, FN, and Col I were detected using immunohistochemistry and immunofluorescence. Primary human nasal fibroblasts were treated with IL-19, then the activation of Smad2/3, NF-κB and relevant pathways, and the expression of FN and Col I were measured.

Results: Expression levels of vimentin, FN, and Col I were significantly increased in nasal tissues from patients with CRSsNP compared with CRSwNP and control subjects. Moreover, IL-19 co-localized with FN and Col Ι in nasal tissues. IL-19-treated fibroblasts had increased production of FN and Col I, which was associated with the activated Smad2/3 and NF-κB pathways. Moreover, Smad2/3 activation was mediated by the NF-κB pathway in IL-19-treated fibroblasts.

Conclusions: IL-19 promotes FN and Col I production via the activated NF-κB-Smad2/3 pathway in fibroblasts, leading to fibrosis and collagen deposition in patients with CRS.

Keywords: Chronic rhinosinusitis; Fibroblast; IL-19; Tissue remodeling.

MeSH terms

  • Chronic Disease
  • Collagen / metabolism
  • Collagen Type I / metabolism
  • Fibroblasts / metabolism
  • Fibronectins / metabolism
  • Humans
  • Interleukins / metabolism
  • NF-kappa B / metabolism
  • Nasal Polyps*
  • Rhinitis*
  • Sinusitis*
  • Smad2 Protein
  • Vimentin

Substances

  • NF-kappa B
  • Fibronectins
  • Vimentin
  • Interleukins
  • Collagen
  • Collagen Type I
  • SMAD2 protein, human
  • Smad2 Protein