Regulation of fibronectin and collagens type I, III and VI by TNF-α, TGF-β, IL-13, and tofacitinib

Regulation of fibronectin and collagens type I, III and VI by TNF-α, TGF-β, IL-13, and tofacitinib

Abstract Understanding how inflammatory cytokines influence profibrogenic wound healing responses in fibroblasts is important for understanding the pathogenesis of fibrosis. TNF-α and IL-13 are key cytokines in Th1 and Th2 immune responses, respectively, while TGF-β1 is the principal pro-fibrotic me...

Full description

Saved in:
Bibliographic Details
Main Authors: Frederik S. Gillesberg, Martin Pehrsson, Anne-Christine Bay-Jensen, Peder Frederiksen, Morten Karsdal, Bent W. Deleuran, Tue W. Kragstrup, Satoshi Kubo, Yoshiya Tanaka, Joachim H. Mortensen
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
Subjects:
Fibro-inflammation
Fibrosis
Wound healing
Collagen
JAK inhibitor
Tofacitinib
Online Access:https://doi.org/10.1038/s41598-024-84151-3
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract Understanding how inflammatory cytokines influence profibrogenic wound healing responses in fibroblasts is important for understanding the pathogenesis of fibrosis. TNF-α and IL-13 are key cytokines in Th1 and Th2 immune responses, respectively, while TGF-β1 is the principal pro-fibrotic mediator. We show that 12-day fibroblast culture with TNF-α or IL-13 induces fibrogenesis, marked by progressively increasing type III and VI collagen formation, and that TGF-β1 co-stimulation amplifies these effects. Tofacitinib substantially reduced the formation of ECM proteins in response to IL-13, while fibrogenesis in response to TNF-α or TGF-β1 was marginally inhibited. The in vitro findings were supported by clinical observations in patients with active rheumatoid arthritis, which had elevated serum type III collagen formation, indicating ongoing fibrogenesis during inflammation. After 48–60 weeks of tofacitinib treatment, type III collagen degradation, aswell as formation, were significantly decreased compared to baseline, highlighting dual anti-inflammatory and anti-fibrogenic effects of tofacitinib. In contrast, other anti-inflammatory treatments including methotrexate, adalimumab and tocilizumab demonstrated anti-inflammatory effects only. Our results highlight fibro-inflammatory profiles associated with TNF-α or IL-13 stimulation, both alone and in combination with TGF-β1, and support the use of tofacitinib as an anti-fibrogenic treatment in chronic inflammatory conditions.
ISSN:2045-2322

Similar Items