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Updated: Jun 20, 2026

An IL-8 Transiently Transgenized Mouse Model for the In Vivo Long-term Monitoring of Inflammatory Responses
08:16

An IL-8 Transiently Transgenized Mouse Model for the In Vivo Long-term Monitoring of Inflammatory Responses

Published on: July 7, 2017

Identification of NR4A2 as a transcriptional activator of IL-8 expression in human inflammatory arthritis

Carol M Aherne1, Jason McMorrow, David Kane

  • 1College of Life Sciences, UCD Veterinary Sciences Centre, University College Dublin, Belfield, Dublin 4, Ireland.

Molecular Immunology
|September 8, 2009
PubMed

Insights

Nuclear receptor NR4A2 targets interleukin-8 (IL-8) in inflammatory arthritis. NR4A2 and NF-kappaB/p65 co-operatively regulate IL-8, impacting inflammatory joint disease progression.

Area of Science:

  • Molecular Biology
  • Immunology
  • Rheumatology

Background:

  • Pro-inflammatory mediators control orphan nuclear receptor NR4A2 expression.
  • NR4A2's role in inflammatory lesions suggests involvement in pathological processes.

Purpose of the Study:

  • Identify chemoattractant protein IL-8 (CXCL8) as an NR4A2 target in human inflammatory arthritis.
  • Examine the mechanism of NR4A2-mediated IL-8 expression modulation.

Main Methods:

  • Analyzed NR4A2 and IL-8 expression in TNF-alpha-activated human synoviocytes.
  • Investigated NR4A2's transcriptional effects on the IL-8 promoter.
  • Assessed NR4A2 interaction with NF-kappaB/p65.
  • Correlated NR4A2 levels with IL-8 expression in arthritis patients.

Main Results:

  • Enhanced IL-8 mRNA and protein expression correlated with NR4A2 changes in synoviocytes.
  • Ectopic NR4A2 expression increased IL-8 levels, potentiated by TNF-alpha.
  • NR4A2 and NF-kappaB/p65 co-operatively enhanced IL-8 transcription via a 39bp promoter region.
  • Reduced NR4A2 levels in patients correlated with altered IL-8 expression.

Conclusions:

  • NR4A2 plays a significant role in modulating IL-8 expression in inflammatory arthritis.
  • Novel transcriptional regulation of IL-8 by TNF-alpha and NR4A2 in joint disease identified.

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