STAT3 and NF-κB signal pathway is required for IL-23-mediated IL-17 production in spontaneous arthritis animal model IL-1 receptor antagonist-deficient mice

Mi La Cho, Jung Won Kang, Young Mee Moon, Hyo Jung Nam, Joo Yeon Jhun, Seong Beom Heo, Hyun Tak Jin, So Youn Min, Ji Hyeon Ju, Kyung Su Park, Young Gyu Cho, Chong Hyeon Yoon, Sung Hwan Park, Young Chul Sung, Ho Youn Kim

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Abstract

IL-23 is a heterodimeric cytokine composed of a p19 subunit and the p40 subunit of IL-12. IL-23 has proinflammatory activity, inducing IL-17 secretion from activated CD4+ T cells and stimulating the proliferation of memory CD4+ T cells. We investigated the pathogenic role of IL-23 in CD4+ T cells in mice lacking the IL-1R antagonist (IL-1Ra -/-), an animal model of spontaneous arthritis. IL-23 was strongly expressed in the inflamed joints of IL-1Ra-/- mice. Recombinant adenovirus expressing mouse IL-23 (rAd/mIL-23) significantly accelerated this joint inflammation and joint destruction. IL-1β further increased the production of IL-23, which induced IL-17 production and OX40 expression in splenic CD4+ T cells of IL-1Ra-/- mice. Blocking IL-23 with anti-p19 Ab abolished the IL-17 production induced by IL-1 in splenocyte cultures. The process of IL-23-induced IL-17 production in CD4+ T cells was mediated via the activation of Jak2, PI3K/Akt, STAT3, and NF-κB, whereas p38 MAPK and AP-1 did not participate in the process. Our data suggest that IL-23 is a link between IL-1 and IL-17. IL-23 seems to be a central proinflammatory cytokine in the pathogenesis of this IL-1Ra-/- model of spontaneous arthritis. Its intracellular signaling pathway could be useful therapeutic targets in the treatment of autoimmune arthritis.

Original languageEnglish (US)
Pages (from-to)5652-5661
Number of pages10
JournalJournal of Immunology
Volume176
Issue number9
StatePublished - May 1 2006

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Interleukin-23
Interleukin-1 Receptors
Interleukin-17
Arthritis
Signal Transduction
Animal Models
Interleukin 1 Receptor Antagonist Protein
T-Lymphocytes
Interleukin-1
Joints
Cytokines
Transcription Factor AP-1
p38 Mitogen-Activated Protein Kinases
Interleukin-12
Phosphatidylinositol 3-Kinases
Adenoviridae
Cell Proliferation
Inflammation

ASJC Scopus subject areas

  • Immunology

Cite this

Cho, M. L., Kang, J. W., Moon, Y. M., Nam, H. J., Jhun, J. Y., Heo, S. B., ... Kim, H. Y. (2006). STAT3 and NF-κB signal pathway is required for IL-23-mediated IL-17 production in spontaneous arthritis animal model IL-1 receptor antagonist-deficient mice. Journal of Immunology, 176(9), 5652-5661.

STAT3 and NF-κB signal pathway is required for IL-23-mediated IL-17 production in spontaneous arthritis animal model IL-1 receptor antagonist-deficient mice. / Cho, Mi La; Kang, Jung Won; Moon, Young Mee; Nam, Hyo Jung; Jhun, Joo Yeon; Heo, Seong Beom; Jin, Hyun Tak; Min, So Youn; Ju, Ji Hyeon; Park, Kyung Su; Cho, Young Gyu; Yoon, Chong Hyeon; Park, Sung Hwan; Sung, Young Chul; Kim, Ho Youn.

In: Journal of Immunology, Vol. 176, No. 9, 01.05.2006, p. 5652-5661.

Research output: Contribution to journalArticle

Cho, ML, Kang, JW, Moon, YM, Nam, HJ, Jhun, JY, Heo, SB, Jin, HT, Min, SY, Ju, JH, Park, KS, Cho, YG, Yoon, CH, Park, SH, Sung, YC & Kim, HY 2006, 'STAT3 and NF-κB signal pathway is required for IL-23-mediated IL-17 production in spontaneous arthritis animal model IL-1 receptor antagonist-deficient mice', Journal of Immunology, vol. 176, no. 9, pp. 5652-5661.
Cho, Mi La ; Kang, Jung Won ; Moon, Young Mee ; Nam, Hyo Jung ; Jhun, Joo Yeon ; Heo, Seong Beom ; Jin, Hyun Tak ; Min, So Youn ; Ju, Ji Hyeon ; Park, Kyung Su ; Cho, Young Gyu ; Yoon, Chong Hyeon ; Park, Sung Hwan ; Sung, Young Chul ; Kim, Ho Youn. / STAT3 and NF-κB signal pathway is required for IL-23-mediated IL-17 production in spontaneous arthritis animal model IL-1 receptor antagonist-deficient mice. In: Journal of Immunology. 2006 ; Vol. 176, No. 9. pp. 5652-5661.
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abstract = "IL-23 is a heterodimeric cytokine composed of a p19 subunit and the p40 subunit of IL-12. IL-23 has proinflammatory activity, inducing IL-17 secretion from activated CD4+ T cells and stimulating the proliferation of memory CD4+ T cells. We investigated the pathogenic role of IL-23 in CD4+ T cells in mice lacking the IL-1R antagonist (IL-1Ra -/-), an animal model of spontaneous arthritis. IL-23 was strongly expressed in the inflamed joints of IL-1Ra-/- mice. Recombinant adenovirus expressing mouse IL-23 (rAd/mIL-23) significantly accelerated this joint inflammation and joint destruction. IL-1β further increased the production of IL-23, which induced IL-17 production and OX40 expression in splenic CD4+ T cells of IL-1Ra-/- mice. Blocking IL-23 with anti-p19 Ab abolished the IL-17 production induced by IL-1 in splenocyte cultures. The process of IL-23-induced IL-17 production in CD4+ T cells was mediated via the activation of Jak2, PI3K/Akt, STAT3, and NF-κB, whereas p38 MAPK and AP-1 did not participate in the process. Our data suggest that IL-23 is a link between IL-1 and IL-17. IL-23 seems to be a central proinflammatory cytokine in the pathogenesis of this IL-1Ra-/- model of spontaneous arthritis. Its intracellular signaling pathway could be useful therapeutic targets in the treatment of autoimmune arthritis.",
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AU - Cho, Mi La

AU - Kang, Jung Won

AU - Moon, Young Mee

AU - Nam, Hyo Jung

AU - Jhun, Joo Yeon

AU - Heo, Seong Beom

AU - Jin, Hyun Tak

AU - Min, So Youn

AU - Ju, Ji Hyeon

AU - Park, Kyung Su

AU - Cho, Young Gyu

AU - Yoon, Chong Hyeon

AU - Park, Sung Hwan

AU - Sung, Young Chul

AU - Kim, Ho Youn

PY - 2006/5/1

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N2 - IL-23 is a heterodimeric cytokine composed of a p19 subunit and the p40 subunit of IL-12. IL-23 has proinflammatory activity, inducing IL-17 secretion from activated CD4+ T cells and stimulating the proliferation of memory CD4+ T cells. We investigated the pathogenic role of IL-23 in CD4+ T cells in mice lacking the IL-1R antagonist (IL-1Ra -/-), an animal model of spontaneous arthritis. IL-23 was strongly expressed in the inflamed joints of IL-1Ra-/- mice. Recombinant adenovirus expressing mouse IL-23 (rAd/mIL-23) significantly accelerated this joint inflammation and joint destruction. IL-1β further increased the production of IL-23, which induced IL-17 production and OX40 expression in splenic CD4+ T cells of IL-1Ra-/- mice. Blocking IL-23 with anti-p19 Ab abolished the IL-17 production induced by IL-1 in splenocyte cultures. The process of IL-23-induced IL-17 production in CD4+ T cells was mediated via the activation of Jak2, PI3K/Akt, STAT3, and NF-κB, whereas p38 MAPK and AP-1 did not participate in the process. Our data suggest that IL-23 is a link between IL-1 and IL-17. IL-23 seems to be a central proinflammatory cytokine in the pathogenesis of this IL-1Ra-/- model of spontaneous arthritis. Its intracellular signaling pathway could be useful therapeutic targets in the treatment of autoimmune arthritis.

AB - IL-23 is a heterodimeric cytokine composed of a p19 subunit and the p40 subunit of IL-12. IL-23 has proinflammatory activity, inducing IL-17 secretion from activated CD4+ T cells and stimulating the proliferation of memory CD4+ T cells. We investigated the pathogenic role of IL-23 in CD4+ T cells in mice lacking the IL-1R antagonist (IL-1Ra -/-), an animal model of spontaneous arthritis. IL-23 was strongly expressed in the inflamed joints of IL-1Ra-/- mice. Recombinant adenovirus expressing mouse IL-23 (rAd/mIL-23) significantly accelerated this joint inflammation and joint destruction. IL-1β further increased the production of IL-23, which induced IL-17 production and OX40 expression in splenic CD4+ T cells of IL-1Ra-/- mice. Blocking IL-23 with anti-p19 Ab abolished the IL-17 production induced by IL-1 in splenocyte cultures. The process of IL-23-induced IL-17 production in CD4+ T cells was mediated via the activation of Jak2, PI3K/Akt, STAT3, and NF-κB, whereas p38 MAPK and AP-1 did not participate in the process. Our data suggest that IL-23 is a link between IL-1 and IL-17. IL-23 seems to be a central proinflammatory cytokine in the pathogenesis of this IL-1Ra-/- model of spontaneous arthritis. Its intracellular signaling pathway could be useful therapeutic targets in the treatment of autoimmune arthritis.

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