Τίτλος:
Chitinases in the salivary glands and circulation of patients with Sjögren's syndrome: Macrophage harbingers of disease severity
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Objective Sjögren's syndrome (SS) is a chronic autoimmune disease of unknown etiology that targets salivary and lacrimal glands and may be accompanied by multiorgan systemic manifestations. To further the understanding of immunopathology associated with SS and identify potential therapeutic targets, we undertook the present study comparing the gene expression profiles of salivary glands with severe inflammation versus those of salivary glands with mild or no disease. Methods Using microarray profiling of salivary gland tissue from patients with SS and control subjects, we identified target genes, which were further characterized in tissue, serum, and cultured cell populations by real-time polymerase chain reaction and protein analysis. Results Among the most highly expressed SS genes were those associated with myeloid cells, including members of the mammalian chitinase family, which had not previously been shown to be associated with exocrinopathies. Both chitinase 3-like protein 1 and chitinase 1, highly conserved chitinase-like glycoproteins (one with enzymatic activity and one lacking enzymatic activity), were evident at the transcriptome level and were detected within inflamed tissue. Chitinases were expressed during monocyte-to-macrophage differentiation and their levels augmented by stimulation with cytokines, including interferon-α (IFNα). Conclusion Because elevated expression of these and other macrophage-derived molecules corresponded with more severe SS, the present observations suggest that macrophages have potential immunopathologic involvement in SS and that the tissue macrophage transcription profile reflects multiple genes induced by IFNα. Copyright © 2011 by the American College of Rheumatology.
Συγγραφείς:
Greenwell-Wild, T.
Moutsopoulos, N.M.
Gliozzi, M.
Kapsogeorgou, E.
Rangel, Z.
Munson, P.J.
Moutsopoulos, H.M.
Wahl, S.M.
Περιοδικό:
Seminars in Arthritis and Rheumatism
Λέξεις-κλειδιά:
alpha interferon; apolipoprotein B messenger RNA editing enzyme catalytic polypeptide 3G; chemokine receptor CXCR3; chitinase; chitinase 1; chitinase 3 like protein 1; gamma interferon; gamma interferon inducible protein 10; glycoprotein; interferon; interleukin 12; interleukin 12 receptor; interleukin 16; interleukin 18; interleukin 2; interleukin 2 receptor; interleukin 23; interleukin 27; interleukin 6 receptor; Janus kinase 2; Janus kinase 3; macrophage inflammatory protein 1alpha; macrophage inflammatory protein 1beta; RANTES; STAT4 protein; STAT5b protein; toll like receptor 8; transcriptome; unclassified drug, adult; article; bone marrow cell; cell culture; cell differentiation; circulation; clinical article; controlled study; disease severity; enzyme activity; gene expression; gene expression profiling; human; human cell; human tissue; immunopathology; macrophage; microarray analysis; monocyte; priority journal; protein analysis; real time polymerase chain reaction; salivary gland; serum; sialoadenitis; Sjoegren syndrome; tissue, Adult; Chitinase; Female; Gene Expression; Humans; Macrophages; Male; Middle Aged; RNA, Messenger; Salivary Glands; Severity of Illness Index; Sjogren's Syndrome
