Interleukin-23 Receptor Gene Polymorphism May Enhance Expression of the IL-23 Receptor, IL-17, TNF-α and IL-6 in Behcet's Disease

PLoS One. 2015 Jul 29;10(7):e0134632. doi: 10.1371/journal.pone.0134632. eCollection 2015.

Abstract

Purpose: Recent studies identified an association between Behcet's disease (BD) and the IL-23R gene polymorphism (rs17375018) in different populations. This study examined whether this IL-23R gene polymorphism is associated with enhanced inflammatory responses.

Methods: We recruited 27 BD patients and 32 controls with three genotypes. Peripheral blood mononuclear cells (PBMCs) were seeded with or without anti-CD3 and CD28. Cells were incubated for 24 hours, and then supernatants were collected and stored at -20◦C until analyzed. Levels of interferon (IFN)-γ, tissue necrosis factor (TNF)-α, interleukin (IL)-17 and IL-6 were detected by ELISA. IL-23R expression was assessed by quantitative real-time polymerase chain reaction (RT-PCR).

Results: The expression of IL-23R was significantly higher in both BD patients and healthy controls with the GG genotype compared to the AG and AA genotype with anti-CD3 and CD28 stimulation (all P-value < 0.05). Among the PBMCs cultured with anti-CD3 and CD28 stimulation, there was an elevated secretion of TNF-α, IL-6 and IL-17 in BD patients and healthy controls with the GG genotype. However, there was no significant change in secretion of IFN- γ in BD patients and healthy controls among the genotype of this IL-23R gene polymorphism.

Conclusions: The results suggest that the GG genotype of the rs17375018 variant in the IL-23R gene enhances pro-inflammatory cytokine responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Behcet Syndrome / genetics*
  • Behcet Syndrome / immunology*
  • Behcet Syndrome / metabolism
  • Case-Control Studies
  • Female
  • Genotype
  • Humans
  • Interleukin-17 / metabolism*
  • Interleukin-6 / metabolism*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Interleukin / genetics*
  • Receptors, Interleukin / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • IL23R protein, human
  • IL6 protein, human
  • Interleukin-17
  • Interleukin-6
  • RNA, Messenger
  • Receptors, Interleukin
  • Tumor Necrosis Factor-alpha

Grants and funding

This work was supported by the National Natural Science Foundation Project of China (81300755), the key project of the Natural Science Foundation of the Higher Educational Bureau of Anhui Province (KJ2013A147), and the Grant of Second Affiliated Hospital of Anhui Medical University (2014BKJ047). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.