<P>Orosomucoid (ORM) is an acute-phase protein that belongs to the immunocalin subfamily, a group of small-molecule-binding proteins with immunomodulatory functions. Little is known about the role of ORM proteins in the CNS. The aim of the prese...
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https://www.riss.kr/link?id=A107430452
2017
-
SCOPUS,SCIE
학술저널
2878-2894(17쪽)
0
상세조회0
다운로드다국어 초록 (Multilingual Abstract)
<P>Orosomucoid (ORM) is an acute-phase protein that belongs to the immunocalin subfamily, a group of small-molecule-binding proteins with immunomodulatory functions. Little is known about the role of ORM proteins in the CNS. The aim of the prese...
<P>Orosomucoid (ORM) is an acute-phase protein that belongs to the immunocalin subfamily, a group of small-molecule-binding proteins with immunomodulatory functions. Little is known about the role of ORM proteins in the CNS. The aim of the present study was to investigate the brain expression of ORM and its role in neuroinflammation. Expression of Orm2, but not Orm1 or Orm3, was highly induced in the mouse brain after systemic injection of lipopolysaccharide (LPS). Plasma levels of ORM2 were also significantly higher in patients with cognitive impairment than in normal subjects. RT-PCR, Western blot, and immunofluorescence analyses revealed that astrocytes are the major cellular sources of ORM2 in the inflamed mouse brain. Recombinant ORM2 protein treatment decreased microglial production of proinflammatory mediators and reduced microglia-mediated neurotoxicity in vitro. LPS-induced microglial activation, proinflammatory cytokines in hippocampus, and neuroinflammation-associated cognitive deficits also decreased as a result of intracerebroventricular injection of recombinant ORM2 protein in vivo. Moreover, lentiviral shRNA-mediated Orm2 knockdown enhanced LPS-induced proinflammatory cytokine gene expression and microglial activation in the hippocampus. Mechanistically, ORM2 inhibited C-C chemokine ligand 4 (CCL4)-induced microglial migration and activation by blocking the interaction of CCL4 with C-C chemokine receptor type 5. Together, the results from our cultured glial cells, mouse neuroinflammation model, and patient studies suggest that ORM2 is a novel mediator of astrocyte-microglial interaction. Wealso report that ORM2 exerts anti-inflammatory effects by modulating microglial activation and migration during brain inflammation. ORM2 can be exploited therapeutically for the treatment of neuroinflammatory diseases.</P>
KNU 의생명융복합 창의인재양성 사업단 (1345274068) / 2017 / BK21플러스사업(0.5) / 권태환 / 경북대학교 / 교육부 / 639,889,000
글리아세포 기반의 치매 바이오마커 발굴 및 개발 (1465022033) / 2016 / 질환극복기술개발 / 석경호 / 경북대학교 산학협력단 / 보건복지부 / 150,000,000
KNU 의생명융복합 창의인재양성 사업단 (1345274068) / 2017 / BK21플러스사업(0.5) / 권태환 / 경북대학교 / 교육부 / 639,889,000
글리아세포 기반의 치매 바이오마커 발굴 및 개발 (1465022033) / 2016 / 질환극복기술개발 / 석경호 / 경북대학교 산학협력단 / 보건복지부 / 150,000,000