Inhibition of Neuroinflammation by AIBP: Spinal Effects upon Facilitated Pain States

Cell Reports
Sarah A WollerYury I Miller

Abstract

Apolipoprotein A-I binding protein (AIBP) reduces lipid raft abundance by augmenting the removal of excess cholesterol from the plasma membrane. Here, we report that AIBP prevents and reverses processes associated with neuroinflammatory-mediated spinal nociceptive processing. The mechanism involves AIBP binding to Toll-like receptor-4 (TLR4) and increased binding of AIBP to activated microglia, which mediates selective regulation of lipid rafts in inflammatory cells. AIBP-mediated lipid raft reductions downregulate LPS-induced TLR4 dimerization, inflammatory signaling, and expression of cytokines in microglia. In mice, intrathecal injections of AIBP reduce spinal myeloid cell lipid rafts, TLR4 dimerization, neuroinflammation, and glial activation. Intrathecal AIBP reverses established allodynia in mice in which pain states were induced by the chemotherapeutic cisplatin, intraplantar formalin, or intrathecal LPS, all of which are pro-nociceptive interventions known to be regulated by TLR4 signaling. These findings demonstrate a mechanism by which AIBP regulates neuroinflammation and suggest the therapeutic potential of AIBP in treating preexisting pain states.

Citations

Apr 16, 2019·Current Opinion in Lipidology·Longhou Fang, Yury I Miller
Dec 22, 2019·Journal of Lipid Research·Yury I MillerTony L Yaksh
Mar 25, 2020·Journal of Lipid Research·Dmitri SviridovYury I Miller
Aug 30, 2019·Journal of Lipid Research·Dmitri Sviridov, Yury I Miller
Aug 14, 2020·Arteriosclerosis, Thrombosis, and Vascular Biology·Hann LowDmitri Sviridov
May 16, 2020·Frontiers in Physiology·Bailey A Loving, Kimberley D Bruce
Jul 10, 2019·Pain Research & Management : the Journal of the Canadian Pain Society = Journal De La Société Canadienne Pour Le Traitement De La Douleur·Jiang BianQing Liu
Nov 25, 2020·Current Atherosclerosis Reports·Xueting QiuLonghou Fang
Aug 11, 2020·Seminars in Cell & Developmental Biology·James Ak LeeScott P Allen
Nov 3, 2020·Frontiers in Immunology·Dmitri SviridovMichael Bukrinsky
Feb 12, 2021·Frontiers in Endocrinology·Beatrice OehlerHeike L Rittner
Mar 16, 2021·Journal of Lipid Research·Dmitri SviridovYury I Miller
Mar 31, 2021·Rheumatic Diseases Clinics of North America·Ejaz M I Pathan, Robert D Inman
Jun 27, 2019·Neuroscience Letters·Q LeyrolleA Nadjar
May 11, 2021·The Journal of Experimental Medicine·Juliana M Navia-PelaezYury I Miller

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