Abstract
PurposeRecent 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.MethodsWe 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).ResultsThe 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.ConclusionsThe results suggest that the GG genotype of the rs17375018 variant in the IL-23R gene enhances pro-inflammatory cytokine responses.
Highlights
Behçet's disease (BD) is a chronic inflammatory disorder characterized as a recurrent vasculitis and a diverse spectrum of clinical manifestations including recurrent oral aphtha, uveitis, multiform skin lesions, and genital ulcerations [1]
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
Among the Peripheral blood mononuclear cells (PBMCs) cultured with anti-CD3 and CD28 stimulation, there was an elevated secretion of tissue necrosis factor (TNF)-α, IL-6 and IL-17 in BD patients and healthy controls with the GG genotype
Summary
Behçet's disease (BD) is a chronic inflammatory disorder characterized as a recurrent vasculitis and a diverse spectrum of clinical manifestations including recurrent oral aphtha, uveitis, multiform skin lesions, and genital ulcerations [1]. Some studies reported that the production of inflammatory cytokines (IFN-γ, TNF-α, IL-6 and IL17) were significantly elevated in BD patients, and the elevated cytokine levels differed among individuals [3,10]. To examine whether this polymorphism is associated with enhanced inflammatory responses, IL-23R expression and inflammatory cytokine production (IFN-γ, TNF-α, IL-6 and IL17) were investigated in healthy individuals and BD patients with three genotypes of rs17375018. These three genotypes of rs17375018 were found to be associated with BD in our previously published study. These three genotypes of rs17375018 were found to be associated with BD in our previously published study. [4]
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