Aligned Expression of IFI16 and STING Genes in RRMS Patients Blood.

Multiple sclerosis (MS) is a chronic neurodegenerative disease of central nervous system. The most common disease phenotype is Relapsing-Remitting MS (RRMS). Beta interferons are the first line of RRMS patients’ treatment. Interferon-inducible protein 16 (IFI16) as a DNA sensing molecule and its downstream complex stimulator of interferon genes (STING) play a critical role in the activation of type I interferons. Hence we aimed to evaluate the expression rate of IFI16 and STING in RRMS patients’ blood under different type of IFNβ treatment.Material and Methods In the present study total of 99 individuals participated. The participants divided into 4 groups: 28 control subjects, 25 new cases of RRMS patients, 25 RRMS patients treated with B1a (B1a), 21 RRMS patients treated with IFNβ-1b (B1b). The EDTA-treated blood samples were taken and transferred at standard conditions to the Cellular and Molecular Research Center of Shahrekord University of Medical Sciences, RNA was extracted and converted to cDNA. To evaluate the expression of IFI16 and STING the Real-Time PCR method using SYBR Green/ROX qPCR mastermix were done. The level of genes expression was measured using -ΔΔCt. The obtained data were analyzed using SPSS v22 software.Results Comparison of the IFI and STING mRNA expression in blood samples in association with gender and age showed no significant difference (p> 0.05). Also evaluation of IFI16 mRNA level revealed that the IFI16 genes expression were remarkably higher in new case group compared to control group, however STING expression did not show any significant difference. The mRNA levels of IFI16 and STING in IFNβ-treated groups was far lower than new case group (p<0.001). Also the genes expression in both IFNβ-treated groups were significantly lower compared to control group (p<0.001). In assessment of IFI16 and STING expressions correlation with age and sex in different research groups, no statistically differences were seen (p> 0.05).Conclusion Perhaps the IFNβ therapy decreases the IFI16 and STING expression in a STING dependent pathway as a negative feedback mechanism for regulation of immune system and suppression of pro-inflammatory cytokines production. Important role of DNA sensing molecules and STING-dependent pathway in MS makes a new insight in future treatment based on STING-direct therapies.

Keywords:

Multiple Sclerosis , IFI16 , IFNβ , STING