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K. Tsubota, A. Higuchi, K. Mishima, H. Inoue, I. Saito; Fractalkine Regulates Tissue-Specific Inflammation in Sjogren’s Syndrome Model Mice. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3659.
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Sjogren’s syndrome (SS) is an organ-specific autoimmune disease caused by the progressive loss of exocrine gland function and is associated with several autoimmune phenomena. Fractalkine is a member of a novel family of mononuclear cell-recruited, cell-surface anchored chemokines, and it has potent chemoattractant activity for T cells and monocytes, and promotes strong adhesion of those leukocytes. In this study, we hypothesized that fractalkine was one of the key molecules to induce lymphocytic infiltration and inflammation in SS.
Semiquantitative reverse transcription (RT)-PCR analysis was performed using cDNA templates synthesized from poly (A)+RNA purified from the lacrimal glands of mice. Immunohistochemical staining with monoclonal antibodies was performed on freshly frozen sections from lacrimal glands of NFS/sld mouse and human Sjogren`s patients. Transgenic mice (TG) of fractalkine were generated to clarify the role of fractalkine in the lacrimal gland.
RT-PCR analysis demonstrated fractalkine was upregulated in thymectomized NFS/sld mice lacrimal glands. Non-thymectomized NFS/sld mice did not show the fractalkine expression, nor did it show the increased lymphocytic infiltration in immunohistochemistry. Fractalkine was detected in the ductal cells in the lacrimal gland of thymectomized-NFS/sld mice in which the lymphocytes were infiltrated. Since fractalkine was expressed in ductal cells in the mouse, we have further studied whether fractalkine could be upregulated with inflammatory stimulation in lacrimal gland epithelial cells. RT-PCR analysis showed that fractalkine was expressed in lacrimal gland epithelial cells stimulated by TNF-alpha. We have evaluated the upregulation of fractalkine in the lacrimal glands of SS patients. Sjogren’s syndrome patients (n = 3) showed the increased fractalkine positive ductal cells and lymphocytes in the lacrimal gland, whereas positive staining was not detected in the lacrimal gland of non-SS dry eye patients. The representative histological finding was observed in the lacrimal gland with inflammatory infiltration in fractalkine TG mice, while infiltrated cells were not seen in littermate lacrimal glands.
Fractalkine is expressed in the lacrimal glands of SS model mice and human SS patients. Fractalkine expression is related to lymphocytic infiltration and inflammation in SS.
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