Activation of GPR35 protects against cerebral ischemia by recruiting monocyte-derived macrophages
Ozayra Sharmin, Ariful Haque Abir, Abdullah Potol, Mahabub Alam, Jewel Banik, A. F. M. Towheedur Rahman, Nuzhat Tarannum, Rasiqh Wadud, Zaki Farhad Habib, Mahbubur Rahman
Abstract
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-6C Lo 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-6C Lo monocytes/macrophages to relay a neuroprotective signal into the ischemic brain.