title: Bee Venom Acupuncture Alleviates Experimental Autoimmune Encephalomyelitis by Upregulating Regulatory T Cells and Suppressing Th1 and Th17 Responses.
abstract: The protective and therapeutic mechanism of bee venom acupuncture (BVA) in neurodegenerative disorders is not clear. We investigated whether treatment with BVA (0.25 and 0.8 mg/kg) at the Zusanli (ST36) acupoints, located lateral from the anterior border of the tibia, has a beneficial effect in a myelin basic protein (MBP)(68-82)-induced acute experimental autoimmune encephalomyelitis (EAE) rat model. Pretreatment (every 3 days from 1 h before immunization) with BVA was more effective than posttreatment (daily after immunization) with BVA with respect to clinical signs (neurological impairment and loss of body weight) of acute EAE rats. Treatment with BVA at the ST36 acupoint in normal rats did not induce the clinical signs. Pretreatment with BVA suppressed demyelination, glial activation, expression of cytokines [interferon (IFN)-γ, IL-17, IL-17A, tumor necrosis factor-alpha (TNF-α), and IL-1β], chemokines [RANTES, monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein (MIP)-1α], and inducible nitric oxide synthase (iNOS), and activation of p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB (p65 and phospho-IκBα) signaling pathways in the spinal cord of acute EAE rats. Pretreatment with BVA decreased the number of CD4(+), CD4(+)/IFN-γ(+), and CD4(+)/IL-17(+) T cells, but increased the number of CD4(+)/Foxp3(+) T cells in the spinal cord and lymph nodes of acute EAE rats. Treatment with BVA at six placebo acupoints (SP9, GB39, and four non-acupoints) did not have a positive effect in acute EAE rats. Interestingly, onset and posttreatment with BVA at the ST36 acupoint markedly attenuated neurological impairment in myelin oligodendrocyte glycoprotein (MOG)(35-55)-induced chronic EAE mice compared to treatment with BVA at six placebo acupoints. Our findings strongly suggest that treatment with BVA with ST36 acupoint could delay or attenuate the development and progression of EAE by upregulating regulatory T cells and suppressing T-helper (Th) 17 and Th1 responses. These results warrant further investigation of BVA as a treatment for autoimmune disorders of the central nervous system.
authors.affiliation: Department of Cancer Preventive Material Development, College of Oriental Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea.|Department of Convergence Medical Science, College of Oriental Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea.
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Lee
authors.affiliation: Department of Cancer Preventive Material Development, College of Oriental Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea.|Department of Convergence Medical Science, College of Oriental Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea.
authors.forename: Minhee
authors.initials: M
authors.lastname: Jang
authors.affiliation: Department of Convergence Medical Science, College of Oriental Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea.|Brain Korea 21 Plus Program, Kyung Hee University, Seoul, 130-701, Republic of Korea.
authors.forename: Jonghee
authors.initials: J
authors.lastname: Choi
authors.affiliation: Department of Physiology, College of Oriental Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea.
authors.forename: Gihyun
authors.initials: G
authors.lastname: Lee
authors.affiliation: Department of Neuroscience and Physiology, School of Dentistry, Seoul National University, Seoul, 110-799, Republic of Korea.|Dental Research Institute, School of Dentistry, Seoul National University, Seoul, 110-799, Republic of Korea.|Brain Korea 21 Plus Program, School of Dentistry, Seoul National University, Seoul, 110-799, Republic of Korea.
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Min
authors.affiliation: Department of Rehabilitation Medicine, College of Oriental Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea.
authors.forename: Won-Seok
authors.initials: WS
authors.lastname: Chung
authors.affiliation: Department of Acupuncture and Moxibustion, College of Oriental Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea.
authors.forename: Jong-In
authors.initials: JI
authors.lastname: Kim
authors.affiliation: College of Veterinary Medicine, Jeju National University, Jeju, 690-756, Republic of Korea.|Applied Radiological Science Institute, Jeju National University, Jeju, 690-756, Republic of Korea.
authors.forename: Youngheun
authors.initials: Y
authors.lastname: Jee
authors.affiliation: Acupuncture and Meridian Science Research Center, College of Oriental Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea.
authors.forename: Younbyoung
authors.initials: Y
authors.lastname: Chae
authors.affiliation: Department of Cancer Preventive Material Development, College of Oriental Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea.
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Neuroscience and Physiology, School of Dentistry, Seoul National University, Seoul, 110-799, Republic of Korea.|Dental Research Institute, School of Dentistry, Seoul National University, Seoul, 110-799, Republic of Korea.|Brain Korea 21 Plus Program, School of Dentistry, Seoul National University, Seoul, 110-799, Republic of Korea.
authors.forename: Sung Joong
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Convergence Medical Science, College of Oriental Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea. ihcho@khu.ac.kr.|Brain Korea 21 Plus Program, Kyung Hee University, Seoul, 130-701, Republic of Korea. ihcho@khu.ac.kr.|Institute of Oriental Medicine, College of Oriental Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea. ihcho@khu.ac.kr.
authors.forename: Ik-Hyun
authors.initials: IH
authors.lastname: Cho
mesh_terms: D015670:Acupuncture Therapy; D000818:Animals; D001514:Bee Venoms / Q000627:therapeutic use*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000150:complications / Q000276:immunology / Q000628:therapy*; D005260:Female; D007111:Immunity, Cellular; D008212:Lymphocyte Depletion; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000473:pathology; D004676:Myelin Basic Protein; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000633:toxicity; D020335:Paraparesis / Q000209:etiology / Q000517:prevention & control; D010446:Peptide Fragments / Q000633:toxicity; D051381:Rats; D011917:Rats, Inbred Lew; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D001514:Bee Venoms; D004676:Myelin Basic Protein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C000614517:myelin basic protein (68-82); C445081:myelin oligodendrocyte glycoprotein (35-55)
keywords: Bee venom acupuncture; Experimental autoimmune encephalomyelitis; Immune cell