title: Altered miR-146a expression in Sjögren's syndrome and its functional role in innate immunity.
abstract: MicroRNAs (miRNAs), small non-coding RNA molecules that post-transcriptionally regulate gene expression, are known to play key roles in regulating immune responses and autoimmunity. We investigated miR-146a expression in Sjögren's syndrome (SjS) patients as well as in the SjS-prone C57BL/6.NOD-Aec1Aec2 mouse model, to elucidate its involvement in SjS pathogenesis. Expression of miR-146a was examined in the PBMCs of 25 SjS patients and ten healthy donors, as well as in PBMCs, salivary and lacrimal glands of SjS-prone mice and WT C57BL/6J mice. Functional assays using THP-1 human monocytes were conducted to determine the biological roles of miR-146a in innate immunity. Expression of miR-146a was significantly increased in SjS patients compared with healthy controls, and was upregulated in the salivary glands and PBMCs of the SjS-prone mouse at both 8 wk (prior to disease onset) and 20 wk (full-blown disease) of age. More importantly, functional analysis revealed roles for miR-146a in increasing phagocytic activity and suppressing inflammatory cytokine production while migration, nitric oxide production and expression of antigen-presenting/costimulatory molecules are not affected in human monocytic THP-1 cells. Taken together, our data suggest that abnormal expression/regulation of microRNAs in innate immunity may contribute to, or be indicative of, the initiation and progression of SjS.
authors.affiliation: Department of Oral and Maxillofacial Diagnostic Sciences, University of Florida College of Dentistry, Gainesville, FL, USA.
authors.forename: Kaleb M
authors.initials: KM
authors.lastname: Pauley
authors.forename: Carol M
authors.initials: CM
authors.lastname: Stewart
authors.forename: Adrienne E
authors.initials: AE
authors.lastname: Gauna
authors.forename: Lauren C
authors.initials: LC
authors.lastname: Dupre
authors.forename: Riya
authors.initials: R
authors.lastname: Kuklani
authors.forename: Annie L
authors.initials: AL
authors.lastname: Chan
authors.forename: Brad A
authors.initials: BA
authors.lastname: Pauley
authors.forename: Westley H
authors.initials: WH
authors.lastname: Reeves
authors.forename: Edward K L
authors.initials: EK
authors.lastname: Chan
authors.forename: Seunghee
authors.initials: S
authors.lastname: Cha
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D017951:Antigen Presentation; D002634:Chemotaxis, Leukocyte; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006801:Humans; D007113:Immunity, Innate; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D009569:Nitric Oxide / Q000096:biosynthesis; D010587:Phagocytosis; D016133:Polymerase Chain Reaction; D012469:Salivary Glands / Q000166:cytology / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D012859:Sjogren's Syndrome / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
chemical_list: D016207:Cytokines; C542542:MIRN146 microRNA, human; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; C534190:Mirn146 microRNA, mouse; D009569:Nitric Oxide