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Increased expression of interferon-λ in minor salivary glands of patients with primary Sjögren's syndrome and its synergic effect with interferon-α on salivary gland epithelial cells

1, 2, 3, 4, 5, 6, 7

  1. Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
  2. Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
  3. Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
  4. Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea.
  5. Departments of Oral and Maxillofacial Diagnostic Sciences and Oral Biology, University of Florida College of Dentistry, Gainesville, USA.
  6. Department of Internal Medicine, Seoul National University Hospital; and WCU Department of Molecular Medicine and Biopharmaceutical Sciences, Medical Research Institute, Seoul, Korea.
  7. Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital; and Department of Internal Medicine, Seoul National University College of Medicine, Korea. yn35@snu.ac.kr

CER10168 Submission on line
Full Papers

Rheumatology Article
Rheumatology Article

 

Abstract

OBJECTIVES:
To investigate the expressions of interferon (IFN)-λs and their receptor, IL28RA, in minor salivary glands (MSG) of pSS patients and their effects on the salivary gland cells.
METHODS:
The expressions of IFN-λs and IL28RA were evaluated in MSG by immunohistochemistry in 15 patients with pSS and in 5 patients with non-SS sicca. Poly(I:C)-induced IL-28A and IL-29 expressions were determined in immortalized human salivary gland acinar (NS-SV-AC) and ductal (NS-SV-DC) cell lines. We assessed the effect of IFN-λs on the expressions of typical interferon-inducible genes, B-cell activating factor (BAFF) and CXCL10, and the synergistic effect of IL-29 and type I or II IFN on their expressions. The serum IL-29 levels were measured in 44 patients with pSS and 22 healthy controls.
RESULTS:
IFN-λs expression was significantly higher in MSG from pSS than from non-SS sicca controls. Poly(I:C) treatment led to the induction of IL-28A and IL-29 in the salivary gland cell lines. In the NS-SV-DC cells, IFN-λ significantly increased the levels of BAFF and CXCL10 in a time and dose-dependent manner. Moreover, there was a synergistic effect between IL-29 and IFN-α in the induction of BAFF and CXCL10 expressions by prolonged STAT1 phosphorylation. However, the serum IL-29 levels were not significantly higher in pSS patients than in healthy controls.
CONCLUSIONS:
Our results suggest the possibility for IFN-λ to play a role by participating local inflammation in the salivary glands of pSS through direct and indirect regulations of the expressions of BAFF and CXCL10 in salivary gland epithelium.

PMID: 28421993 [PubMed]

Received: 11/12/2016 - Accepted : 06/03/2017 - In Press: 18/04/2017