title: Activation of the adenosine A2A receptor attenuates experimental autoimmune encephalomyelitis and is associated with increased intracellular calcium levels.
abstract: Multiple sclerosis (MS) is a common autoimmune disease that inevitably causes inflammatory nerve demyelination. However, an effective approach to prevent its course is still lacking and urgently needed. Recently, the adenosine A2A receptor (A2AR) has emerged as a novel inflammation regulator. Manipulation of A2AR activity may suppress the MS process and protect against nerve damage. To test this hypothesis, we treated murine experimental autoimmune encephalomyelitis (EAE), a model for MS, with the selective A2AR agonist, CGS21680 (CGS). We evaluated the effects of CGS on the pathological features of EAE progression, including CNS cellular infiltration, inflammatory cytokine expression, lymphocyte proliferation, and cell surface markers. Treatment with CGS significantly suppressed specific lymphocyte proliferation, reduced infiltration of CD4(+) T lymphocytes, and attenuated the expression of inflammatory cytokines, which in turn inhibited the EAE progression. For the first time, we demonstrate that CGS can increase the intracellular calcium concentration ([Ca(2+)]i) in murine lymphocytes, which may be the mechanism underlying the suppressive effects of CGS-induced A2AR activation on EAE progression. Our findings strongly suggest that A2AR is a potential therapeutic target for MS and provide insight into the mechanism of action of A2AR agonists, which may offer a therapeutic option for this disease.
authors.affiliation: Department of Neurobiology, Neurobiology Key Laboratory, Harbin Medical University, Education Department of Heilongjiang Province, Harbin, Heilongjiang 150086, China.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Neurobiology, Neurobiology Key Laboratory, Harbin Medical University, Education Department of Heilongjiang Province, Harbin, Heilongjiang 150086, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Zou
authors.affiliation: Department of Neurobiology, Neurobiology Key Laboratory, Harbin Medical University, Education Department of Heilongjiang Province, Harbin, Heilongjiang 150086, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Department of Neurobiology, Neurobiology Key Laboratory, Harbin Medical University, Education Department of Heilongjiang Province, Harbin, Heilongjiang 150086, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Neurobiology, Neurobiology Key Laboratory, Harbin Medical University, Education Department of Heilongjiang Province, Harbin, Heilongjiang 150086, China.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Neurobiology, Neurobiology Key Laboratory, Harbin Medical University, Education Department of Heilongjiang Province, Harbin, Heilongjiang 150086, China.
authors.forename: Qingfei
authors.initials: Q
authors.lastname: Kong
authors.affiliation: Department of Neurobiology, Neurobiology Key Laboratory, Harbin Medical University, Education Department of Heilongjiang Province, Harbin, Heilongjiang 150086, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Mu
authors.affiliation: Department of Neurobiology, Neurobiology Key Laboratory, Harbin Medical University, Education Department of Heilongjiang Province, Harbin, Heilongjiang 150086, China.
authors.forename: Sihan
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Neurobiology, Neurobiology Key Laboratory, Harbin Medical University, Education Department of Heilongjiang Province, Harbin, Heilongjiang 150086, China.
authors.forename: Guangyou
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Neurobiology, Neurobiology Key Laboratory, Harbin Medical University, Education Department of Heilongjiang Province, Harbin, Heilongjiang 150086, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Neurobiology, Neurobiology Key Laboratory, Harbin Medical University, Education Department of Heilongjiang Province, Harbin, Heilongjiang 150086, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurobiology, Neurobiology Key Laboratory, Harbin Medical University, Education Department of Heilongjiang Province, Harbin, Heilongjiang 150086, China.
authors.forename: Jiaying
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Neurobiology, Neurobiology Key Laboratory, Harbin Medical University, Education Department of Heilongjiang Province, Harbin, Heilongjiang 150086, China.
authors.forename: Pengqi
authors.initials: P
authors.lastname: Yin
authors.affiliation: Department of Psychiatry, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China. Electronic address: zxllili@163.com.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Neurobiology, Neurobiology Key Laboratory, Harbin Medical University, Education Department of Heilongjiang Province, Harbin, Heilongjiang 150086, China; Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, Harbin, Heilongjiang 150086, China. Electronic address: lihl@hrbmu.edu.cn.
authors.forename: Hulun
authors.initials: H
authors.lastname: Li
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D005260:Female; D007155:Immunologic Factors / Q000494:pharmacology*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism*; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008810:Mice, Inbred C57BL; D009186:Myelin Sheath / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010627:Phenethylamines / Q000494:pharmacology*; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D012720:Severity of Illness Index; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D058908:Adenosine A2 Receptor Agonists; D007155:Immunologic Factors; D010627:Phenethylamines; D043705:Receptor, Adenosine A2A; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D000241:Adenosine; D002118:Calcium
keywords: adenosine A2A receptor; experimental autoimmune encephalomyelitis; intracellular calcium; multiple sclerosis