Activation of GPR35 protects against cerebral ischemia by recruiting monocyte-derived macrophages.

Scientific Reports
Ozayra SharminMahbubur Rahman

Abstract

Pamoic acid is a potent ligand for G protein Coupled Receptor 35 (GPR35) and exhibits antinociceptive property. GPR35 activation leads to increased energy utilization and the expression of anti-inflammatory genes. However, its role in brain disorders, especially in stroke, remains unexplored. Here we show in a mouse model of stroke that GPR35 activation by pamoic acid is neuroprotective. Pharmacological inhibition of GPR35 reveals that pamoic acid reduces infarcts size in a GPR35 dependent manner. The flowcytometric analysis shows the expression of GPR35 on the infiltrating monocytes/macrophages and neutrophils in the ischemic brain. Pamoic acid treatment results in a preferential increment of noninflammatory Ly-6CLo monocytes/macrophages in the ischemic brain along with the reduced neutrophil counts. The neuroprotective effect of GPR35 activation depends on protein kinase B (Akt) and p38 MAPK. Together we conclude that GPR35 activation by pamoic acid reprograms Ly-6CLo monocytes/macrophages to relay a neuroprotective signal into the ischemic brain.

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Citations

Oct 20, 2020·ACS Pharmacology & Translational Science·Tezz QuonGraeme Milligan

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Methods Mentioned

BETA
flowcytometry
Fluorescence
flow cytometry
MDA
pharmacotherapy
enzyme-linked immunosorbent assay
ELISA

Software Mentioned

ImageJ

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