Spontaneous resolution of acute gouty arthritis is associated with rapid induction of the anti-inflammatory factors TGFβ1, IL-10 and soluble TNF receptors and the intracellular cytokine negative regulators CIS and SOCS3

Yu Hsuan Chen, Song Chou Hsieh, Wei Yu Chen, Ko Jen Li, Cheng Han Wu, Po Chang Wu, Chang Youh Tsai, Chia Li Yu

Research output: Contribution to journalArticle

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Abstract

Objective: The molecular basis for spontaneous resolution of acute gouty arthritis (GA) remains unclear. The hypothesis that extracellular and intracellular mechanisms play roles in resolving acute GA was tested. Methods: Synovial fluid (SF) levels of transforming growth factor β1 (TGFβ1), interleukin 1 (IL-1) receptor antagonist (IL-1ra), IL-10 and soluble tumour necrosis factor (TNF) receptor I (sTNFRI) and II (sTNFRII) were measured by ELISA in patients with acute GA and osteoarthritis (OA). Monosodium urate (MSU) crystal-stimulated RAW264.7 mouse macrophages were analysed for cytokine inducible SH2-containing protein (CIS) and suppressors of cytokine signalling (SOCS) 1-7 mRNA expression by reverse transcription (RT)-PCR. Immunohistochemical analysis, quantitative PCR and immunoblotting were performed to detect CIS and SOCS3 expression in synovial tissue, SF mononuclear cells (SFMCs) from patients with GA and MSU crystalstimulated monocyte-derived macrophages from healthy donors. CIS overexpression and small interfering RNA-mediated knockdown in RAW264.7 cells were used to investigate the role of CIS in resolving MSU crystal-induced acute inflammation. Results: SF levels of anti-inflammatory molecules TGFβ1, IL-1ra, IL-10 and sTNFR-I/II were significantly elevated in GA compared to OA. CIS and SOCS3 were upregulated in the synovium and SFMCs from acute GA and MSU crystal-stimulated monocyte-derived macrophages and RAW264.7 cells. CIS overexpression in RAW264.7 cells attenuated MSU crystal-induced IL-1β and TNFα but enhanced TGFβ1 production via increased binding of signal transducer and activator of transcription 3 (STAT3) to the TGFβ1 promoter. Conversely, CIS knockdown reversed the effect of CIS overexpression, resulting in enhanced IL-1β and TNFα but reduced TGFβ1 production in MSU crystal-stimulated RAW264.7 cells. Conclusions: Increased production of TGFβ1, IL-1ra, IL-10 and sTNFR-I/II and upregulation of intracellular CIS and SOCS3 expression are associated with spontaneous resolution of acute GA.

Original languageEnglish
Pages (from-to)1655-1663
Number of pages9
JournalAnnals of the Rheumatic Diseases
Volume70
Issue number9
DOIs
Publication statusPublished - Sep 2011

Fingerprint

Gouty Arthritis
Tumor Necrosis Factor Receptors
Transforming Growth Factors
Interleukin-10
Anti-Inflammatory Agents
Cytokines
Uric Acid
Interleukin-1 Receptors
Macrophages
Synovial Fluid
Crystals
Interleukin-1
Osteoarthritis
Fluids
Tumor Necrosis Factor-alpha
cytokine inducible SH2-containing protein
STAT3 Transcription Factor
Polymerase Chain Reaction
Synovial Membrane
Transcription

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Allergy

Cite this

Spontaneous resolution of acute gouty arthritis is associated with rapid induction of the anti-inflammatory factors TGFβ1, IL-10 and soluble TNF receptors and the intracellular cytokine negative regulators CIS and SOCS3. / Chen, Yu Hsuan; Hsieh, Song Chou; Chen, Wei Yu; Li, Ko Jen; Wu, Cheng Han; Wu, Po Chang; Tsai, Chang Youh; Yu, Chia Li.

In: Annals of the Rheumatic Diseases, Vol. 70, No. 9, 09.2011, p. 1655-1663.

Research output: Contribution to journalArticle

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abstract = "Objective: The molecular basis for spontaneous resolution of acute gouty arthritis (GA) remains unclear. The hypothesis that extracellular and intracellular mechanisms play roles in resolving acute GA was tested. Methods: Synovial fluid (SF) levels of transforming growth factor β1 (TGFβ1), interleukin 1 (IL-1) receptor antagonist (IL-1ra), IL-10 and soluble tumour necrosis factor (TNF) receptor I (sTNFRI) and II (sTNFRII) were measured by ELISA in patients with acute GA and osteoarthritis (OA). Monosodium urate (MSU) crystal-stimulated RAW264.7 mouse macrophages were analysed for cytokine inducible SH2-containing protein (CIS) and suppressors of cytokine signalling (SOCS) 1-7 mRNA expression by reverse transcription (RT)-PCR. Immunohistochemical analysis, quantitative PCR and immunoblotting were performed to detect CIS and SOCS3 expression in synovial tissue, SF mononuclear cells (SFMCs) from patients with GA and MSU crystalstimulated monocyte-derived macrophages from healthy donors. CIS overexpression and small interfering RNA-mediated knockdown in RAW264.7 cells were used to investigate the role of CIS in resolving MSU crystal-induced acute inflammation. Results: SF levels of anti-inflammatory molecules TGFβ1, IL-1ra, IL-10 and sTNFR-I/II were significantly elevated in GA compared to OA. CIS and SOCS3 were upregulated in the synovium and SFMCs from acute GA and MSU crystal-stimulated monocyte-derived macrophages and RAW264.7 cells. CIS overexpression in RAW264.7 cells attenuated MSU crystal-induced IL-1β and TNFα but enhanced TGFβ1 production via increased binding of signal transducer and activator of transcription 3 (STAT3) to the TGFβ1 promoter. Conversely, CIS knockdown reversed the effect of CIS overexpression, resulting in enhanced IL-1β and TNFα but reduced TGFβ1 production in MSU crystal-stimulated RAW264.7 cells. Conclusions: Increased production of TGFβ1, IL-1ra, IL-10 and sTNFR-I/II and upregulation of intracellular CIS and SOCS3 expression are associated with spontaneous resolution of acute GA.",
author = "Chen, {Yu Hsuan} and Hsieh, {Song Chou} and Chen, {Wei Yu} and Li, {Ko Jen} and Wu, {Cheng Han} and Wu, {Po Chang} and Tsai, {Chang Youh} and Yu, {Chia Li}",
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T1 - Spontaneous resolution of acute gouty arthritis is associated with rapid induction of the anti-inflammatory factors TGFβ1, IL-10 and soluble TNF receptors and the intracellular cytokine negative regulators CIS and SOCS3

AU - Chen, Yu Hsuan

AU - Hsieh, Song Chou

AU - Chen, Wei Yu

AU - Li, Ko Jen

AU - Wu, Cheng Han

AU - Wu, Po Chang

AU - Tsai, Chang Youh

AU - Yu, Chia Li

PY - 2011/9

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N2 - Objective: The molecular basis for spontaneous resolution of acute gouty arthritis (GA) remains unclear. The hypothesis that extracellular and intracellular mechanisms play roles in resolving acute GA was tested. Methods: Synovial fluid (SF) levels of transforming growth factor β1 (TGFβ1), interleukin 1 (IL-1) receptor antagonist (IL-1ra), IL-10 and soluble tumour necrosis factor (TNF) receptor I (sTNFRI) and II (sTNFRII) were measured by ELISA in patients with acute GA and osteoarthritis (OA). Monosodium urate (MSU) crystal-stimulated RAW264.7 mouse macrophages were analysed for cytokine inducible SH2-containing protein (CIS) and suppressors of cytokine signalling (SOCS) 1-7 mRNA expression by reverse transcription (RT)-PCR. Immunohistochemical analysis, quantitative PCR and immunoblotting were performed to detect CIS and SOCS3 expression in synovial tissue, SF mononuclear cells (SFMCs) from patients with GA and MSU crystalstimulated monocyte-derived macrophages from healthy donors. CIS overexpression and small interfering RNA-mediated knockdown in RAW264.7 cells were used to investigate the role of CIS in resolving MSU crystal-induced acute inflammation. Results: SF levels of anti-inflammatory molecules TGFβ1, IL-1ra, IL-10 and sTNFR-I/II were significantly elevated in GA compared to OA. CIS and SOCS3 were upregulated in the synovium and SFMCs from acute GA and MSU crystal-stimulated monocyte-derived macrophages and RAW264.7 cells. CIS overexpression in RAW264.7 cells attenuated MSU crystal-induced IL-1β and TNFα but enhanced TGFβ1 production via increased binding of signal transducer and activator of transcription 3 (STAT3) to the TGFβ1 promoter. Conversely, CIS knockdown reversed the effect of CIS overexpression, resulting in enhanced IL-1β and TNFα but reduced TGFβ1 production in MSU crystal-stimulated RAW264.7 cells. Conclusions: Increased production of TGFβ1, IL-1ra, IL-10 and sTNFR-I/II and upregulation of intracellular CIS and SOCS3 expression are associated with spontaneous resolution of acute GA.

AB - Objective: The molecular basis for spontaneous resolution of acute gouty arthritis (GA) remains unclear. The hypothesis that extracellular and intracellular mechanisms play roles in resolving acute GA was tested. Methods: Synovial fluid (SF) levels of transforming growth factor β1 (TGFβ1), interleukin 1 (IL-1) receptor antagonist (IL-1ra), IL-10 and soluble tumour necrosis factor (TNF) receptor I (sTNFRI) and II (sTNFRII) were measured by ELISA in patients with acute GA and osteoarthritis (OA). Monosodium urate (MSU) crystal-stimulated RAW264.7 mouse macrophages were analysed for cytokine inducible SH2-containing protein (CIS) and suppressors of cytokine signalling (SOCS) 1-7 mRNA expression by reverse transcription (RT)-PCR. Immunohistochemical analysis, quantitative PCR and immunoblotting were performed to detect CIS and SOCS3 expression in synovial tissue, SF mononuclear cells (SFMCs) from patients with GA and MSU crystalstimulated monocyte-derived macrophages from healthy donors. CIS overexpression and small interfering RNA-mediated knockdown in RAW264.7 cells were used to investigate the role of CIS in resolving MSU crystal-induced acute inflammation. Results: SF levels of anti-inflammatory molecules TGFβ1, IL-1ra, IL-10 and sTNFR-I/II were significantly elevated in GA compared to OA. CIS and SOCS3 were upregulated in the synovium and SFMCs from acute GA and MSU crystal-stimulated monocyte-derived macrophages and RAW264.7 cells. CIS overexpression in RAW264.7 cells attenuated MSU crystal-induced IL-1β and TNFα but enhanced TGFβ1 production via increased binding of signal transducer and activator of transcription 3 (STAT3) to the TGFβ1 promoter. Conversely, CIS knockdown reversed the effect of CIS overexpression, resulting in enhanced IL-1β and TNFα but reduced TGFβ1 production in MSU crystal-stimulated RAW264.7 cells. Conclusions: Increased production of TGFβ1, IL-1ra, IL-10 and sTNFR-I/II and upregulation of intracellular CIS and SOCS3 expression are associated with spontaneous resolution of acute GA.

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