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

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.

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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

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Funding

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

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Correspondence to Chafia Touil-Boukoffa.

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Benchabane, S., Belkhelfa, M., Belguendouz, H. et al. Interferon-β inhibits inflammatory responses mediators via suppression of iNOS signaling pathway in PBMCs from patients with primary Sjögren’s syndrome. Inflammopharmacol 26, 1165–1174 (2018). https://doi.org/10.1007/s10787-018-0499-4

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Keywords

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