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Inflammopharmacology

, Volume 26, Issue 5, pp 1165–1174 | Cite as

Interferon-β inhibits inflammatory responses mediators via suppression of iNOS signaling pathway in PBMCs from patients with primary Sjögren’s syndrome

  • Sarah Benchabane
  • Mourad Belkhelfa
  • Houda Belguendouz
  • Sourour Zidi
  • Abdelhalim Boudjelida
  • Pierre Youinou
  • Chafia Touil-BoukoffaEmail author
Original Article

Abstract

Background

Primary Sjögren’s syndrome (pSS) represents a chronic, systemic autoimmune disorder, characterized by lymphocytic infiltration of exocrine glands, inducing compromised secretory function and tissue destruction. Increasing evidence had revealed that inflammatory mediators, such as nitric oxide (NO) and pro-inflammatory cytokines, are critical in the development and perpetuation of pSS systemic manifestations. In our current study, we aimed to investigate the ex vivo immunomodulatory effect of interferon (IFN)-β on iNOS expression, as well as on pro-inflammatory (tumor necrosis factor (TNF)-α, interleukin (IL)-6) and immunoregulatory (IL-10) cytokine production. Furthermore, we examined potential associations between the influence of IFN-β treatment on NO production, and pSS clinical and serological manifestations.

Methods

In 41 pSS patients documented for their clinical and serological features, NO and cytokines levels were measured by the Griess method and enzyme-linked immunosorbent assay, respectively. Inducible nitric oxide synthase expression was analyzed by fluorescence immunostaining assay, using peripheral blood mononuclear cells (PBMCs) isolated from healthy controls and pSS patients.

Results

Our results revealed a strong down-modulating effect of IFN-β in the secretion of pro-inflammatory mediators including TNF-α, IL-6, and NO production. Interestingly, IFN-β exerts an increase in IL-10 levels. The most suppressive effect exerted by IFN-β on NO production was importantly reported for patients with neurological manifestation. This immunomodulatory effect of IFN-β on NO production is highly related to the decrease of inducible nitric oxide synthase (iNOS) expression.

Conclusion

Our findings highlight a consistent ex vivo inhibitory effect of IFN-β on pro-inflammatory cytokine production and NO pathway in pSS patients. Our data suggest that IFN-β could represent a potential candidate for targeting inflammation during pSS.

Keywords

Primary Sjögren’s syndrome Interferon-β Immunomodulation Nitric oxide IL-6 TNF-α IL-10 

Abbreviations

IFN-β

Interferon-β

IL-6

Interleukin 6

IL-10

Interleukin 10

IL-17A

Interleukin 17A

iNOS

Inducible NO synthase

LPS

Lipopolysaccharide

NF-кB

Nuclear factor kappa B

NO

Nitric oxide

PBMC

Peripheral blood mononuclear cells

pSS

Primary Sjögren’s syndrome

SS

Sjögren’s syndrome

Notes

Funding

This work was supported by national thematic research agency in development health science (ATRSS, ex ANDRS), Project Code N°43-ANDRS-2011.

Compliance with ethical standards

Conflict of interest

The authors report no declarations of interest.

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Sarah Benchabane
    • 1
    • 2
  • Mourad Belkhelfa
    • 1
  • Houda Belguendouz
    • 1
  • Sourour Zidi
    • 1
    • 3
    • 4
  • Abdelhalim Boudjelida
    • 5
  • Pierre Youinou
    • 6
  • Chafia Touil-Boukoffa
    • 1
    Email author
  1. 1.Laboratory of Cellular and Molecular Biology (LBCM), Cytokines and NO Synthases Group, Faculty of Biological SciencesUniversity of Sciences and Technology Houari Boumediene (USTHB)AlgiersAlgeria
  2. 2.Department of Biology and Cellular Physiology, Faculty of Biological SciencesSaad Dahlab’s University of BlidaBlidaAlgeria
  3. 3.Department of BiologyUniversity of GuelmaGuelmaAlgeria
  4. 4.Badji Mokhtar UniversityAnnabaAlgeria
  5. 5.Internal Medicine DepartmentMaillot HospitalAlgiersAlgeria
  6. 6.Laboratory of Excellence (Labex) IGO, and INSERM ERI29European University of BrittanyBrestFrance

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