Cytokine mRNA expression in salivary gland biopsies of Sjögren's syndrome.
Sjögren's syndrome is a human autoimmune disease characterized by lymphocytic infiltration of salivary and lacrimal glands, hypergammaglobulinemia, and specific autoantibodies. The accessibility of the salivary gland to biopsy provides an opportunity to study cytokine mRNA expression at the site of organ-specific immune damage. Using reverse transcriptase and a quantitative PCR to measure cytokine mRNA, we found Sjögren's syndrome: 1) salivary gland CD4+ T cells produce over 40-fold more IL-2, IFN-gamma, and IL-10 mRNA than peripheral blood CD4+ T cells from the same patient or from normal controls; 2) salivary gland CD4+ T cells produced little IL-4 and IL-5 mRNA immediately after elution from the salivary gland, although these mRNAs could be induced by mitogen stimulation of Sjögren's syndrome salivary gland lymphocytes in vitro; 3) salivary gland epithelial cells produced over 40-fold more IL-1 alpha, IL-6, and TNF-alpha mRNA than epithelial cells from individuals with histologically normal salivary glands. Increased levels of IL-1 alpha, IL-6, IL-10, TNF-alpha, and IFN-gamma cytokines were found by ELISA assay in the saliva of Sjögren's syndrome patients, indicating that the elevated mRNA levels detected in their glandular tissue by PCR correlate with local protein synthesis. Our results demonstrate that CD4+ cells in the salivary glands of Sjögren's syndrome patients exhibit mRNA expression that is distinct from previously described Th1 and Th2 lymphocytes in mice or cytokines reported in other human autoimmune or allergic diseases. Also, we found that salivary gland epithelial cells may participate in the pathogenesis of Sjögren's syndrome biopsy by producing cytokines (IL-1 alpha, IL-6, and TNF-alpha).
Fox
R I
RI
Department of Rheumatology and Immunology, Scripps Clinic and Research Foundation, La Jolla, CA 92037.
Kang
H I
HI
Ando
D
D
Abrams
J
J
Pisa
E
E
D001402:B-Lymphocytes / Q000378:metabolism; D001483:Base Sequence; D001706:Biopsy; D002460:Cell Line; D016207:Cytokines / Q000032:analysis / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis*; D012469:Salivary Glands / Q000378:metabolism*; D012859:Sjogren's Syndrome / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism
D016207:Cytokines; D012333:RNA, Messenger