Retinoid acid inhibits IL-1-induced iNOS, COX-2 and chemokine production in human chondrocytes

Li Feng Hung, Jenn Haung Lai, Leou Chyr Lin, Shyu Jye Wang, Tsung Yun Hou, Deh Ming Chang, Chun Chin T. Liang, Ling Jun Ho

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

This study aims to investigate the effects and mechanisms of all-trans retinoic acid (t-RA) on interleukin(IL)-1-induced production of several inflammatory mediators in human chondrocytes. The cartilage from OA patients receiving total knee or total hip replacement was obtained and chondrocytes were prepared. Chemokine concentrations were measured by ELISA. The expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was determined by Western blotting and/or RT/PCR. Nitrite levels were measured by Griess assays. The DNA-binding activity and transcriptional activity of activator protein-1 (AP-1) were measured by electrophoresis mobility shift assay and luciferase assay. We showed that t-RA suppressed IL-1-induced release of chemokines, including regulated upon activation, normal T cell expressed and secreted (RANTES), monocyte chemoattractant protein 2 (MCP-2), macrophage inflammatory protein-1alpha (MIP-1α) and MIP-1β. Four different retinoid derivatives all preserved inhibitory effects albeit the potency was different. t-RA potently suppressed IL-1-induced expression of iNOS and COX-2 and production of nitric oxide and prostaglandin E2. In consistent with the results in primary chondrocytes, t-RA down-regulated IL-1-induced AP-1 DNA binding activity and transcriptional activity in a human fibroblast-like (commercially labeled as chondrocyte) cell line. By examining the effect of a c-jun N-terminal kinase (JNK) specific inhibitor, we showed that the suppression of JNK-AP-1 signaling was enough to inhibit IL-1-induced production of chemokines and activation of iNOS and COX-2 pathways. Collectively, our results raise a therapeutic option that intra-articular administration of retinoid derivatives at 10-1000 nanomolar concentrations may be effective to suppress the progression of inflammatory OA.

Original languageEnglish
Pages (from-to)675-693
Number of pages19
JournalImmunological Investigations
Volume37
Issue number7
DOIs
Publication statusPublished - Oct 1 2008
Externally publishedYes

Fingerprint

Retinoids
Nitric Oxide Synthase Type II
Cyclooxygenase 2
Chondrocytes
Interleukin-1
Chemokines
Tretinoin
Transcription Factor AP-1
Acids
Macrophage Inflammatory Proteins
Chemokine CCL8
Hip Replacement Arthroplasties
JNK Mitogen-Activated Protein Kinases
DNA
Electrophoretic Mobility Shift Assay
Nitrites
Luciferases
Dinoprostone
Cartilage
Electrophoresis

Keywords

  • Chemokines
  • Chondrocytes
  • Cyclooxygenase-2
  • Inducible nitric oxide synthase
  • Osteoarthritis
  • Retinoic acid

ASJC Scopus subject areas

  • Immunology

Cite this

Hung, L. F., Lai, J. H., Lin, L. C., Wang, S. J., Hou, T. Y., Chang, D. M., ... Ho, L. J. (2008). Retinoid acid inhibits IL-1-induced iNOS, COX-2 and chemokine production in human chondrocytes. Immunological Investigations, 37(7), 675-693. https://doi.org/10.1080/08820130802307237

Retinoid acid inhibits IL-1-induced iNOS, COX-2 and chemokine production in human chondrocytes. / Hung, Li Feng; Lai, Jenn Haung; Lin, Leou Chyr; Wang, Shyu Jye; Hou, Tsung Yun; Chang, Deh Ming; Liang, Chun Chin T.; Ho, Ling Jun.

In: Immunological Investigations, Vol. 37, No. 7, 01.10.2008, p. 675-693.

Research output: Contribution to journalArticle

Hung, LF, Lai, JH, Lin, LC, Wang, SJ, Hou, TY, Chang, DM, Liang, CCT & Ho, LJ 2008, 'Retinoid acid inhibits IL-1-induced iNOS, COX-2 and chemokine production in human chondrocytes', Immunological Investigations, vol. 37, no. 7, pp. 675-693. https://doi.org/10.1080/08820130802307237
Hung, Li Feng ; Lai, Jenn Haung ; Lin, Leou Chyr ; Wang, Shyu Jye ; Hou, Tsung Yun ; Chang, Deh Ming ; Liang, Chun Chin T. ; Ho, Ling Jun. / Retinoid acid inhibits IL-1-induced iNOS, COX-2 and chemokine production in human chondrocytes. In: Immunological Investigations. 2008 ; Vol. 37, No. 7. pp. 675-693.
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abstract = "This study aims to investigate the effects and mechanisms of all-trans retinoic acid (t-RA) on interleukin(IL)-1-induced production of several inflammatory mediators in human chondrocytes. The cartilage from OA patients receiving total knee or total hip replacement was obtained and chondrocytes were prepared. Chemokine concentrations were measured by ELISA. The expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was determined by Western blotting and/or RT/PCR. Nitrite levels were measured by Griess assays. The DNA-binding activity and transcriptional activity of activator protein-1 (AP-1) were measured by electrophoresis mobility shift assay and luciferase assay. We showed that t-RA suppressed IL-1-induced release of chemokines, including regulated upon activation, normal T cell expressed and secreted (RANTES), monocyte chemoattractant protein 2 (MCP-2), macrophage inflammatory protein-1alpha (MIP-1α) and MIP-1β. Four different retinoid derivatives all preserved inhibitory effects albeit the potency was different. t-RA potently suppressed IL-1-induced expression of iNOS and COX-2 and production of nitric oxide and prostaglandin E2. In consistent with the results in primary chondrocytes, t-RA down-regulated IL-1-induced AP-1 DNA binding activity and transcriptional activity in a human fibroblast-like (commercially labeled as chondrocyte) cell line. By examining the effect of a c-jun N-terminal kinase (JNK) specific inhibitor, we showed that the suppression of JNK-AP-1 signaling was enough to inhibit IL-1-induced production of chemokines and activation of iNOS and COX-2 pathways. Collectively, our results raise a therapeutic option that intra-articular administration of retinoid derivatives at 10-1000 nanomolar concentrations may be effective to suppress the progression of inflammatory OA.",
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