title: Aspirin regulates SNARE protein expression and phagocytosis in dendritic cells.
abstract: Since being introduced globally as Aspirin in 1899, acetylsalicylic acid (ASA) has been widely used as an analgesic, immune-regulatory, anti-pyretic and anti-thrombotic drug. ASA and its metabolite, salicylate, were also reported to be able to modulate antigen presenting functions of dendritic cells (DC). However, the intracellular targets of ASA in DC are still poorly understood. Since phagocytosis is the initial step taken by antigen-presenting cells in the uptake of antigens for processing and presentation, ASA might exerts its immune-regulatory effects by regulating phagocytosis. Here we show that ASA inhibits phagocytosis and modulates expression of endosomal SNAREs, such as Vti1a, Vti1b, VAMP-3, VAMP-8 and Syn-8 (but not syn-6 and syn-16) in DC. We further show that the phagocytic inhibitory effect of ASA is dependent on the expression of Vti1a and Vti1b. Consistently, Vti1a and Vti1b localize to the phagosomes and up-regulation of Vti1a and Vti1b inhibits phagocytosis in DC. Our results suggest that ASA modulates phagocytosis in part through the control of endosomal SNARE protein expression and localization in DC. All experiments were performed using either a murine DC line (DC2.4) or primary DC derived from murine bone marrow cells.
authors.affiliation: Laboratory of Membrane Trafficking & Immunoregulation, Department of Microbiology and Immunology Program, Yong Loo Lin School of Medicine, National University of Singapore, Republic of Singapore.
authors.forename: Deyu Tarika
authors.initials: DT
authors.lastname: Cai
authors.forename: Yong Hou Sunny
authors.initials: YH
authors.lastname: Ho
authors.forename: Kher Hsin
authors.initials: KH
authors.lastname: Chiow
authors.forename: Seok Hui
authors.initials: SH
authors.lastname: Wee
authors.forename: Yulan
authors.initials: Y
authors.lastname: Han
authors.forename: Meng Teng
authors.initials: MT
authors.lastname: Peh
authors.forename: Siew Heng
authors.initials: SH
authors.lastname: Wong
mesh_terms: D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D002460:Cell Line; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D018274:Electroporation; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D051379:Mice; D008810:Mice, Inbred C57BL; D010587:Phagocytosis / Q000187:drug effects*; D010588:Phagosomes / Q000235:genetics; D016133:Polymerase Chain Reaction; D050766:Qb-SNARE Proteins / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D050766:Qb-SNARE Proteins; C491418:Vti1a protein, mouse; C491415:Vti1b protein, mouse; D001241:Aspirin