Interleukin-22, a member of the IL-10 subfamily, induces inflammatory responses in colonic subepithelial myofibroblasts

Akira Andoh, Zhuobin Zhang, Osamu Inatomi, Sanae Fujino, Yasuyuki Deguchi, Yoshio Araki, Tomoyuki Tsujikawa, Katsuyuki Kitoh, Shokei Kim-Mitsuyama, Atsushi Takayanagi, Nobuyoshi Shimizu, Yoshihide Fujiyama

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Abstract

Background & Aims: Interleukin (IL)-22, a member of the IL-10 subfamily, is a recently identified T-cell-derived cytokine. We investigated IL-22 expression in the inflamed mucosa of patients with inflammatory bowel disease (IBD) and analyzed its biologic activities in human colonic subepithelial myofibroblasts (SEMFs). Methods: Mucosal IL-22 expression was evaluated by immunohistochemical procedures. The effects of IL-22 on colonic SEMFs were investigated by cDNA microarrays, Northern blots, enzyme-linked immunosorbent assay, and electrophoretic gel mobility shift assays (EMSAs). Results: IL-22 was not detectable in normal colonic mucosa. In IBD mucosa, IL-22 expression was detectable in CD4-positive T cells. IL-22-positive cells were increased in ulcerative colitis and even more so in Crohn's disease. IL-22 receptor expression colocalized with a marker of SEMFs. IL-22 did not modulate SEMF proliferation and collagen synthesis. cDNA microarray analyses demonstrated that, in colonic SEMFs, IL-22 increased the messenger RNA (mRNA) expression of inflammatory cytokines (IL-6, IL-8, IL-11, and leukemia inhibitory factor [LIF]), chemokines, and matrix metalloproteinases. IL-22 induced an activation of nuclear factor (NF)-κB and activating protein (AP)-1 within 1 hour, and a blockade of NF-κB and AP-1 activation markedly reduced IL-22 induction of IL-6, IL-8, IL-11, and LIF mRNA. MAP-kinase inhibitors (PD98059, U0216, and SB202190) significantly reduced IL-22 induction of cytokine secretion. The combination of either IL-17 plus IL-22 or IL-19 plus IL-22 additively up-regulated cytokine secretion. Conclusions: IL-22 derived from activated T cells acts on SEMFs to elicit expression of proinflammatory cytokines and matrix-degrading molecules indicating proinflammatory/remodeling roles in IBD.

Original languageEnglish
Pages (from-to)969-984
Number of pages16
JournalGastroenterology
Volume129
Issue number3
DOIs
Publication statusPublished - 2005 Sep

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Myofibroblasts
Interleukin-10
Cytokines
Inflammatory Bowel Diseases
Interleukin-11
Leukemia Inhibitory Factor
Mucous Membrane
interleukin-22
Oligonucleotide Array Sequence Analysis
T-Lymphocytes
Interleukin-8
Interleukin-6
Messenger RNA
Interleukin-17
Interleukins
Electrophoretic Mobility Shift Assay
Microarray Analysis
Matrix Metalloproteinases
Ulcerative Colitis
Chemokines

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Interleukin-22, a member of the IL-10 subfamily, induces inflammatory responses in colonic subepithelial myofibroblasts. / Andoh, Akira; Zhang, Zhuobin; Inatomi, Osamu; Fujino, Sanae; Deguchi, Yasuyuki; Araki, Yoshio; Tsujikawa, Tomoyuki; Kitoh, Katsuyuki; Kim-Mitsuyama, Shokei; Takayanagi, Atsushi; Shimizu, Nobuyoshi; Fujiyama, Yoshihide.

In: Gastroenterology, Vol. 129, No. 3, 09.2005, p. 969-984.

Research output: Contribution to journalArticle

Andoh, A, Zhang, Z, Inatomi, O, Fujino, S, Deguchi, Y, Araki, Y, Tsujikawa, T, Kitoh, K, Kim-Mitsuyama, S, Takayanagi, A, Shimizu, N & Fujiyama, Y 2005, 'Interleukin-22, a member of the IL-10 subfamily, induces inflammatory responses in colonic subepithelial myofibroblasts', Gastroenterology, vol. 129, no. 3, pp. 969-984. https://doi.org/10.1053/j.gastro.2005.06.071
Andoh, Akira ; Zhang, Zhuobin ; Inatomi, Osamu ; Fujino, Sanae ; Deguchi, Yasuyuki ; Araki, Yoshio ; Tsujikawa, Tomoyuki ; Kitoh, Katsuyuki ; Kim-Mitsuyama, Shokei ; Takayanagi, Atsushi ; Shimizu, Nobuyoshi ; Fujiyama, Yoshihide. / Interleukin-22, a member of the IL-10 subfamily, induces inflammatory responses in colonic subepithelial myofibroblasts. In: Gastroenterology. 2005 ; Vol. 129, No. 3. pp. 969-984.
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T1 - Interleukin-22, a member of the IL-10 subfamily, induces inflammatory responses in colonic subepithelial myofibroblasts

AU - Andoh, Akira

AU - Zhang, Zhuobin

AU - Inatomi, Osamu

AU - Fujino, Sanae

AU - Deguchi, Yasuyuki

AU - Araki, Yoshio

AU - Tsujikawa, Tomoyuki

AU - Kitoh, Katsuyuki

AU - Kim-Mitsuyama, Shokei

AU - Takayanagi, Atsushi

AU - Shimizu, Nobuyoshi

AU - Fujiyama, Yoshihide

PY - 2005/9

Y1 - 2005/9

N2 - Background & Aims: Interleukin (IL)-22, a member of the IL-10 subfamily, is a recently identified T-cell-derived cytokine. We investigated IL-22 expression in the inflamed mucosa of patients with inflammatory bowel disease (IBD) and analyzed its biologic activities in human colonic subepithelial myofibroblasts (SEMFs). Methods: Mucosal IL-22 expression was evaluated by immunohistochemical procedures. The effects of IL-22 on colonic SEMFs were investigated by cDNA microarrays, Northern blots, enzyme-linked immunosorbent assay, and electrophoretic gel mobility shift assays (EMSAs). Results: IL-22 was not detectable in normal colonic mucosa. In IBD mucosa, IL-22 expression was detectable in CD4-positive T cells. IL-22-positive cells were increased in ulcerative colitis and even more so in Crohn's disease. IL-22 receptor expression colocalized with a marker of SEMFs. IL-22 did not modulate SEMF proliferation and collagen synthesis. cDNA microarray analyses demonstrated that, in colonic SEMFs, IL-22 increased the messenger RNA (mRNA) expression of inflammatory cytokines (IL-6, IL-8, IL-11, and leukemia inhibitory factor [LIF]), chemokines, and matrix metalloproteinases. IL-22 induced an activation of nuclear factor (NF)-κB and activating protein (AP)-1 within 1 hour, and a blockade of NF-κB and AP-1 activation markedly reduced IL-22 induction of IL-6, IL-8, IL-11, and LIF mRNA. MAP-kinase inhibitors (PD98059, U0216, and SB202190) significantly reduced IL-22 induction of cytokine secretion. The combination of either IL-17 plus IL-22 or IL-19 plus IL-22 additively up-regulated cytokine secretion. Conclusions: IL-22 derived from activated T cells acts on SEMFs to elicit expression of proinflammatory cytokines and matrix-degrading molecules indicating proinflammatory/remodeling roles in IBD.

AB - Background & Aims: Interleukin (IL)-22, a member of the IL-10 subfamily, is a recently identified T-cell-derived cytokine. We investigated IL-22 expression in the inflamed mucosa of patients with inflammatory bowel disease (IBD) and analyzed its biologic activities in human colonic subepithelial myofibroblasts (SEMFs). Methods: Mucosal IL-22 expression was evaluated by immunohistochemical procedures. The effects of IL-22 on colonic SEMFs were investigated by cDNA microarrays, Northern blots, enzyme-linked immunosorbent assay, and electrophoretic gel mobility shift assays (EMSAs). Results: IL-22 was not detectable in normal colonic mucosa. In IBD mucosa, IL-22 expression was detectable in CD4-positive T cells. IL-22-positive cells were increased in ulcerative colitis and even more so in Crohn's disease. IL-22 receptor expression colocalized with a marker of SEMFs. IL-22 did not modulate SEMF proliferation and collagen synthesis. cDNA microarray analyses demonstrated that, in colonic SEMFs, IL-22 increased the messenger RNA (mRNA) expression of inflammatory cytokines (IL-6, IL-8, IL-11, and leukemia inhibitory factor [LIF]), chemokines, and matrix metalloproteinases. IL-22 induced an activation of nuclear factor (NF)-κB and activating protein (AP)-1 within 1 hour, and a blockade of NF-κB and AP-1 activation markedly reduced IL-22 induction of IL-6, IL-8, IL-11, and LIF mRNA. MAP-kinase inhibitors (PD98059, U0216, and SB202190) significantly reduced IL-22 induction of cytokine secretion. The combination of either IL-17 plus IL-22 or IL-19 plus IL-22 additively up-regulated cytokine secretion. Conclusions: IL-22 derived from activated T cells acts on SEMFs to elicit expression of proinflammatory cytokines and matrix-degrading molecules indicating proinflammatory/remodeling roles in IBD.

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