Upregulated IRAK1 and IRAK4 promoting the production of IFN-γ and IL-17 in Behcet's disease.

Abstract

To investigate the expression and function of IRAK1 and IRAK4 involved in the development of Behcet's disease. Twenty-eight Behcet's patients and thirty-two normal subjects were involved in this study. The mRNA levels of IRAK1 and IRAK4 from active Behcet's patients, inactive Behcet's patients and normal controls were detected using real-time quantitative PCR. CD4+T cells were extracted from peripheral blood mononuclear cells of active Behcet's patients and normal controls. After coculturing IRAK1/4 inhibitor with CD4+T cells in the presence of rIL-18 protein or rIL-1β protein for 3days, the proliferation of CD4+T cells was measured using a modified MTT assay. Meanwhile, the levels of IFN-γ and IL-17 were detected by enzyme-linked immunosorbent assay. The mRNA levels of IRAK1 and IRAK4 were both significantly increased in active Behcet's patients compared with those of inactive Behcet's patients and normal subjects. However, there was no difference of IRAK1 mRNA level or the IRAK4 mRNA level between the inactive Behcet's patients and normal controls. After coculturing with IRAK1/4 inhibitor, the proliferation of the CD4+T cells was inhibited both in active Behcet's patients and in normal controls. Meanwhile, the expression of IFN-γ and IL-17 was also suppressed by IRAK1/4 inhibitor both in active Behcet's patients and in normal subjects. The high mRNA levels of IRAK1 and IRAK4 were correlated with the development of Behcet's disease, which suggested that IRAK1 and IRAK4 might participate in the pathogenesis of Behcet's disease. The inhibitory function of IRAK1/4 inhibitor prompts that it may be a new therapeutic target for treating this blindness disease.