title: Interleukin(IL)-36α and IL-36γ Induce Proinflammatory Mediators from Human Colonic Subepithelial Myofibroblasts.
abstract: BACKGROUND
  Interleukin (IL)-36 cytokines are recently reported member of the IL-1 cytokine family. However, there is little information regarding the association between IL-36 cytokines and gut inflammation. In the present study, we investigated the biological activity of IL-36α and IL-36γ using human colonic subepithelial myofibroblasts (SEMFs).
  
  
  METHODS
  The mRNA expression and the protein expression of target molecules in SEMFs were evaluated using real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The intracellular signaling of IL-36 cytokines was analyzed using Western blot analysis and small interfering RNAs (siRNAs) specific for MyD88 adaptor proteins (MyD88 and IRAK1) and NF-κB p65.
  
  
  RESULTS
  IL-36α and IL-36γ significantly enhanced the secretion of IL-6 and CXC chemokines (CXCL1, CXCL2, and CXCL8) by SEMFs. The combination of IL-36α/γ and IL-17A or of IL-36α/γ and tumor necrosis factor-α showed a synergistic effect on the induction of IL-6 and CXC chemokines. The mRNA expression of proinflammatory mediators induced by IL-36α and/or IL-36γ was significantly suppressed by transfection of siRNA for MyD88 or IRAK1. Both inhibitors of mitogen activated protein kinases and siRNAs specific for NF-κBp65 significantly reduced the expression of IL-6 and CXC chemokines induced by IL-36α and/or IL-36γ.
  
  
  CONCLUSIONS
  These results suggest that IL-36α and IL-36γ contribute to gut inflammation through the induction of proinflammatory mediators.
authors.affiliation: Department of Medicine, Shiga University of Medical Science , Otsu , Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Kanda
authors.affiliation: Department of Medicine, Shiga University of Medical Science , Otsu , Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nishida
authors.affiliation: Department of Medicine, Shiga University of Medical Science , Otsu , Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Department of Medicine, Shiga University of Medical Science , Otsu , Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Hidaka
authors.affiliation: Department of Medicine, Shiga University of Medical Science , Otsu , Japan.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Imaeda
authors.affiliation: Department of Medicine, Shiga University of Medical Science , Otsu , Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Inatomi
authors.affiliation: Department of Medicine, Shiga University of Medical Science , Otsu , Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Bamba
authors.affiliation: Department of Medicine, Shiga University of Medical Science , Otsu , Japan.
authors.forename: Mitsushige
authors.initials: M
authors.lastname: Sugimoto
authors.affiliation: Department of Medicine, Shiga University of Medical Science , Otsu , Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Andoh
keywords: colon; inflammatory bowel disease; interleukin-1; interleukin-36; myofibroblasts