The microglial innate immune protein PGLYRP1 mediates neuroinflammation and consequent behavioral changes
Anup Bhusal,
Jae-Hong Kim,
Seung-Chan Kim,
Eun Mi Hwang,
Hoon Ryu,
Md. Sekendar Ali,
Seung-Chun Park,
Won-Ha Lee,
Kyoungho Suk
Affiliations
Anup Bhusal
Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea; BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea
Jae-Hong Kim
Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea; Brain Korea 21 Four KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea
Seung-Chan Kim
Brain Science Institute, Korea Institute of Science and Technology, Seoul, Republic of Korea
Eun Mi Hwang
Brain Science Institute, Korea Institute of Science and Technology, Seoul, Republic of Korea
Hoon Ryu
Center for Neuroscience, Brain Science Institute, Korea Institute of Science and Technology, Seoul, Republic of Korea
Md. Sekendar Ali
Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea; Laboratory of Veterinary Pharmacokinetics and Pharmacodynamics, Institute for Veterinary Biomedical Science, College of Veterinary Medicine, Kyungpook National University, Daegu, Republic of Korea
Seung-Chun Park
Laboratory of Veterinary Pharmacokinetics and Pharmacodynamics, Institute for Veterinary Biomedical Science, College of Veterinary Medicine, Kyungpook National University, Daegu, Republic of Korea; Cardiovascular Research Institute, Kyungpook National University, Daegu, Republic of Korea
Won-Ha Lee
School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea; Brain Science and Engineering Institute, Kyungpook National University, Daegu 41944, Republic of Korea
Kyoungho Suk
Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea; BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea; Brain Science and Engineering Institute, Kyungpook National University, Daegu 41944, Republic of Korea; Corresponding author
Summary: Peptidoglycan recognition protein 1 (PGLYRP1) is a pattern-recognition protein that mediates antibacterial actions and innate immune responses. Its expression and role in neuroinflammatory conditions remain unclear. We observed the upregulation of PGLYRP1 in inflamed human and mouse spinal cord and brain, with microglia being the primary cellular source. Experiments using a recombinant PGLYRP1 protein show that PGLYRP1 potentiates reactive gliosis, neuroinflammation, and consequent behavioral changes in multiple animal models of neuroinflammation. Furthermore, shRNA-mediated knockdown of Pglyrp1 gene expression attenuates this inflammatory response. In addition, we identify triggering receptor expressed on myeloid cell-1 (TREM1) as an interaction partner of PGLYRP1 and demonstrate that PGLYRP1 promotes neuroinflammation through the TREM1-Syk-Erk1/2-Stat3 axis in cultured glial cells. Taken together, our results reveal a role for microglial PGLYRP1 as a neuroinflammation mediator. Finally, we propose that PGLYRP1 is a potential biomarker and therapeutic target in various neuroinflammatory diseases.
