Journal of Gastroenterology

, Volume 42, Issue 9, pp 746–753

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

Authors

  • Yuhki Yagi
    • Department of Internal MedicineShiga University of Medical Science
  • Akira Andoh
    • Department of Internal MedicineShiga University of Medical Science
  • Osamu Inatomi
    • Department of Internal MedicineShiga University of Medical Science
  • Tomoyuki Tsujikawa
    • Department of Internal MedicineShiga University of Medical Science
  • Yoshihide Fujiyama
    • Department of Internal MedicineShiga University of Medical Science
Alimentary Tract

DOI: 10.1007/s00535-007-2091-3

Cite this article as:
Yagi, Y., Andoh, A., Inatomi, O. et al. J Gastroenterol (2007) 42: 746. doi:10.1007/s00535-007-2091-3

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 cellsMAP kinaseinflammationIBD
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Copyright information

© Springer-Verlag Tokyo 2007