Title:Aligned Expression of IFI16 and STING Genes in RRMS Patients’ Blood
Volume: 20
Issue: 6
Author(s): Sobhan Helbi, Behnam Ravanbakhsh, Mohammad Karimi, Wesam Kooti*Nahid Jivad*
Affiliation:
- Lung Diseases and Allergy Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj,Iran
- Department of Neurology, Faculty of Medicine, Shahrekord University of Medical Sciences, Shahrekord,Iran
Keywords:
Multiple sclerosis, IFI16, IFNβ, STING, chronic disease, beta Interferons.
Abstract:
Objective: Multiple sclerosis (MS) is a chronic neurodegenerative disease of the 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 a different type of IFNβ treatment.
Methods: In the present study, 99 individuals participated. The participants were divided into 4 groups:
28 control subjects, 25 new cases of RRMS patients, 25 RRMS patients treated with IFNβ-1a (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 into cDNA. To evaluate the expression of
IFI16 and STING, the Real-Time PCR method using SYBR Green/ROX qPCR master mix was performed
done. The level of genes expression was measured using 2–ΔΔCt method. 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 differences (p>0.05). Also, the evaluation of IFI16 mRNA level
revealed that the IFI16 genes’ expressions were remarkably higher in the new case group compared to
the control group, however, STING expression did not show any significant difference. The mRNA
levels of IFI16 and STING in IFNβ-treated groups were significantly lower than the new case group
(p<0.001). Also, the genes’ expressions in both the IFNβ-treated groups were significantly lower compared
to the control group (p<0.001). In the assessment of the correlation of IFI16 and STING expressions
with age and sex in different research groups, no statistically significant differences were seen
(p>0.05).
Conclusion: Perhaps the IFNβ therapy decreases the IFI16 and STING expression in a STINGdependent
pathway as a negative feedback mechanism for regulation of the immune system and suppression
of pro-inflammatory cytokines production. The important role of DNA sensing molecules and
STING-dependent pathway in MS gives a new insight into future treatment based on STING-direct
therapies.
