Download 2016 department of medicine research day

2016 DEPARTMENT OF MEDICINE RESEARCH DAY
Title of Poster: A Membrane Glycerolipid Protects Against Immune-Mediated Liver
Inflammation via Mobilization and Migration of Myeloid-Derived Suppressor Cells
Presenter: Ramesh Halder, PhD
Division: Rheumatology
☒ Faculty ☐ Fellow ☐ Resident ☐ Post-doc Research Fellow ☐ Graduate Student ☐ Medical Student ☐Other
Principal Investigator/Mentor: Ram R. Singh, M.D.
Thematic Poster Category:
Atherosclerosis
Co-Investigators: Priti Prasad, Cynthia Tran
Infections, Injury and Repair, Inflammation, Host Defense, Immunology, Hemostasis and
Abstract
A Membrane Glycerolipid Protects Against Immune-Mediated Liver Inflammation via Mobilization and
Migration of Myeloid-Derived Suppressor Cells
Ramesh Halder, Priti Prasad, Cynthia Tran, Ram Raj Singh
Autoimmunity and Tolerance Laboratory, Division of Rheumatology, Department of Medicine, David
Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA 90095, USA
Membrane lipids function as essential components of biological membranes, as signaling molecules,
and as energy storage molecules. Phosphatidic acid (PA) is a vital membrane lipid that serves as a
precursor for the synthesis of all acylglycerol lipids in the cell. PA serves as a lipid second messenger
that modulates diverse intracellular signaling. PA participates in a wide range of cellular processes,
including vesicular trafficking, cytoskeletal organization, secretion, endocytosis, exocytosis, cell
proliferation, differentiation, migration and survival. Administration of large doses of PA in animals (1
mg per mouse) can increase serum levels of pro-inflammatory cytokines. PA can do so by stimulating
the production of pro-inflammatory cytokines including TNF-α, IL-1β, and IL-6 in macrophages
through the Akt and mTOR pathways. Thus, PA may play facilitate the initiation of the host
inflammatory response. Here, we examined the effect of PA in an inflammatory condition. Contrary to
the above reports, PA protected against immune mediated liver inflammation induced by concanavalin
A and reduced pro-inflammatory cytokines but increased anti-inflammatory cytokine interleukin-10 in
the liver. PA did so by inducing the mobilization and migration of monocytic myeloid-derived
suppressor cells that upon adoptive transfer protected against autoimmune liver inflammation. Our
novel observations indicating immune protective functions of PA may have wide implications for a
variety of conditions with altered lipid metabolism and inflammation such as atherosclerosis and
autoimmune disease and conditions with local or systemic alterations in PA such as osteoarthritis and
Alzheimer’s disease.
Acknowledgement: Supported by NHLBI R21 and NIAID R01 to RRS, NIAMS F31 to CT, RRF
Preceptorship and Gina Finzi fellowship to PP.