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Journal of Gastroenterology

, Volume 42, Issue 9, pp 746–753 | Cite as

Inflammatory responses induced by interleukin-17 family members in human colonic subepithelial myofibroblasts

  • Yuhki Yagi
  • Akira Andoh
  • Osamu Inatomi
  • Tomoyuki Tsujikawa
  • Yoshihide Fujiyama
Alimentary Tract

Abstract

Background

We investigated the potential role of interleukin (IL)-17 family members (IL-17A to IL-17F) in the induction of inflammatory responses in human colonic subepithelial myofibroblasts (SEMFs).

Methods

The expression of the inflammatory cytokines IL-6, IL-8, leukemia inhibitory factor (LIF), and matrix metalloproteinases (MMP)-1 and MMP-3 were evaluated by enzyme-linked immunosorbent assay and Northern blotting. Activation of mitogen-activated protein kinase (MAPK) was assessed by immunoblotting.

Results

IL-17A and IL-17F significantly enhanced IL-6, IL-8, LIF, MMP-1, and MMP-3 secretion. The effects of IL-17A were relatively stronger than those induced by IL-17F. The effects of IL-17B, IL-17C, IL-17D, and IL-17E were modest as compared with those induced by IL-17A and IL-17F. Both IL-17A and IL-17F augmented IL-1β-induced secretion of IL-6, IL-8, LIF, MMP-1, and MMP-3. A similar augmentation was also observed in tumor necrosis factor (TNF)-α-induced cytokine and MMP secretion. IL-17A and IL-17F rapidly induced phosphorylation of extracellular signal-regulated kinases (ERK) 1/2, p38 MAPKs, and c-Jun-NH2-terminal kinase (JNK) as early as 15 min after stimulation. Inhibitors for ERK (PD98059 and U0216) and p38 MAPK (SB203580) significantly reduced the IL-17F-induced IL-6, IL-8, LIF, MMP-1, and MMP-3 secretion.

Conclusions

Among IL-17 family members, IL-17A and IL-17F strongly stimulate human colonic SEMFs, inducing inflammatory responses.

Key words

Th17 cells MAP kinase inflammation IBD 

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Copyright information

© Springer-Verlag Tokyo 2007

Authors and Affiliations

  • Yuhki Yagi
    • 1
  • Akira Andoh
    • 1
  • Osamu Inatomi
    • 1
  • Tomoyuki Tsujikawa
    • 1
  • Yoshihide Fujiyama
    • 1
  1. 1.Department of Internal MedicineShiga University of Medical ScienceOtsuJAPAN

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