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.

Keywords::

• Dendritic cells
• SNARE
• aspirin

Acknowledgements

We thank Dr Kevin Tan Shyong-wei for the generous gift of GFP-E. coli, and Dr Kenneth Rock for the DC2.4 cell line. We also thank Drs Lim Kah Leong, Lu Jinhua, and Michael Kemeny and members of the Membrane Trafficking and Immunoregulation Research Laboratory for critical reading of the manuscript.

Declaration of interest: This work was supported by research grants from the Academic Research Fund-NUS (R182-000-092-112 to S.H.W) and the Academic Research Council-Ministry of Education, Singapore (R182-000-099-112 to S.H.W). The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.