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

• Published in: Scientific reports Vol. 10; no. 1; p. 9400
• Main Authors: Sharmin, Ozayra, Abir, Ariful Haque, Potol, Abdullah, Alam, Mahabub, Banik, Jewel, Rahman, A.F.M. Towheedur, Tarannum, Nuzhat, Wadud, Rasiqh, Habib, Zaki Farhad, Rahman, Mahbubur
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10.06.2020; Nature Publishing Group
• Subjects: 631/378; 631/378/1689; 692/699/375/365; 692/699/375/534; Acids; AKT protein; Animals; Brain - drug effects; Brain - metabolism; Brain Ischemia - drug therapy; Brain Ischemia - metabolism; Cerebral Infarction - drug therapy; Cerebral Infarction - metabolism; Disease Models, Animal; Energy utilization; Humanities and Social Sciences; Inflammation; Ischemia; Kinases; Leukocytes (neutrophilic); Ligands; Ly-6 antigen; Macrophages; Macrophages - drug effects; Macrophages - metabolism; Male; MAP kinase; Mice; Monocytes; Monocytes - drug effects; Monocytes - metabolism; multidisciplinary; Naphthols - pharmacology; Neuroprotection; Neuroprotective Agents - pharmacology; Neutrophils - drug effects; Neutrophils - metabolism; Pain perception; Receptors, G-Protein-Coupled - metabolism; Science; Science (multidisciplinary); Stroke; Stroke - drug therapy; Stroke - metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-66417-8

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.