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

Sarah A. Woller, Soo Ho Choi, Eun Jung An, Hann Low, Dina A. Schneider, Roshni Ramachandran, Jungsu Kim, Yun Soo Bae, Dmitri Sviridov, Maripat Corr, Tony L. Yaksh, Yury I. Miller

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

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. Woller et al. report that ApoA-I binding protein (AIBP) selectively regulates, via TLR4 binding, cholesterol removal and normalization of lipid rafts in inflamed microglia. Spinal delivery of AIBP reduces neuroinflammation and prevents and reverses neuropathic pain states, such as chemotherapy-induced peripheral neuropathy, with an effect sustained for >2 months.

Original languageEnglish
Pages (from-to)2667-2677
Number of pages11
JournalCell Reports
Volume23
Issue number9
DOIs
StatePublished - 29 May 2018

Keywords

  • AIBP
  • TLR4
  • allodynia
  • chemotherapy
  • cholesterol
  • chronic pain
  • inflammation
  • lipid rafts
  • neuroinflammation
  • neuropathic pain

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