MMP-9 Inhibition Suppresses Interferon- γ-Induced CXCL10 Production in Human Salivary Gland Ductal Cells

In this study, we used LSG sections from pSS patients and human salivary gland cell lines to investigate the relati onship between CXCL10 and MMP-9. Immunofluorescence analyses revealed that CXCL10 and MMP-9 were co-expressed in the LSG of pSS patients, particularly in expanded ductal cells. Furthermore, RT-qPCR analyses on human salivary gland ductal NS-SV-DC cells confirmed thatCXCL10 expression was induced by interferon (IFN)- γ, whereas that ofMMP9 was stimulated by IFN- α, tumor necrosis factor-α, and interleukin-1β. Remarkably, MMP-9 inhibition in IFN-γ-stimulated NS-SV-DC cells significantly decreased CXCL10 mRNA and secreted protein levels. Further analyses established that MMP-9 inhibition in IFN-γ-stimulated NS-SV-DC cells decreased STAT1 phosphorylation and hence suppressed IFN-γ signaling. Collectively, these results suggest that in addition to its reported role in the destruction of acinar structures, MMP-9 is involved in the IFN-γ-induced production of CXCL10 in pSS lesions. We believe that our findings open the door to the development of nove l treatments for pSS, based on the modulation of MMP-9 activity.
Source: Inflammation - Category: Allergy & Immunology Source Type: research