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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.

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.

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