1. Academic Validation
  2. Activation of GPR35 protects against cerebral ischemia by recruiting monocyte-derived macrophages

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

  • Sci Rep. 2020 Jun 10;10(1):9400. doi: 10.1038/s41598-020-66417-8.
Ozayra Sharmin  # 1 Ariful Haque Abir  # 1 Abdullah Potol 1 2 Mahabub Alam 1 Jewel Banik 1 3 A F M Towheedur Rahman 1 4 Nuzhat Tarannum 1 Rasiqh Wadud 1 5 Zaki Farhad Habib 1 6 Mahbubur Rahman 7
Affiliations

Affiliations

  • 1 Laboratory of Pharmacology, Department of Pharmaceutical Sciences, School of Health & Life Sciences, North South University, Bashundhra R/A, Dhaka, 1229, Bangladesh.
  • 2 Faculty of Medicine, Friedrich Schiller University Jena, 07743, Jena, Germany.
  • 3 Deptartment of Neurobiology & Developmental Sciences, College of Medicine, UAMS, 4301W. Markham St., Little Rock, AR, 72205, USA.
  • 4 Milwaukee Institute of Drug Discovery, Department of chemistry and Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, WI, 53211, USA.
  • 5 Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge, CB3 0ES, UK.
  • 6 Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, UK.
  • 7 Laboratory of Pharmacology, Department of Pharmaceutical Sciences, School of Health & Life Sciences, North South University, Bashundhra R/A, Dhaka, 1229, Bangladesh. rahman.mahbubur@northsouth.edu.
  • # Contributed equally.
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.

Figures
Products