title: The effects of D3R on TLR4 signaling involved in the regulation of METH-mediated mast cells activation.
abstract: Accumulating studies have revealed that the dopamine D3 receptor (D3R) plays an important role in methamphetamine (METH) addiction. However, the action of D3R on METH-mediated immune response and the underlying mechanism remain unclear. Mast cells (MCs) are currently identified as effector cells in many processes of immune responses, and MC activation is induced by various stimuli such as lipopolysaccharide (LPS). Moreover, CD117 and FcεRI are known as MC markers due to their specific expression in MCs. To investigate the effects of D3R on METH-mediated alteration of LPS-induced MCs activation and the underlying mechanism, in this study, we examined the expression of CD117 and FcεRI in the intestines of wild-type (D3R(+/+)) and D3R-deficient (D3R(-/-)) mice. We also measured the production of MC-derived cytokines, including TNF-α, IL-6, IL-4, IL-13 and CCL-5, in the bone marrow-derived mast cells (BMMCs) of WT and D3R(-/-) mice. Furthermore, we explored the effects of D3R on METH-mediated TLR4 and downstream MAPK and NF-κB signaling induced by LPS in mouse BMMCs. We found that METH suppressed MC activation induced by LPS in the intestines of D3R(+/)mice. In contrast, LPS-induced MC activation was less affected by METH in D3R(-/-) mice. Furthermore, METH altered LPS-induced cytokine production in BMMCs of D3R(+/+) mice but not D3R(-/-) mice. D3R was also involved in METH-mediated modulation of LPS-induced expression of TLR4 and downstream MAPK and NF-κB signaling molecules in mouse BMMCs. Taken together, our findings demonstrate that the effect of D3R on TLR4 signaling may be implicated in the regulation of METH-mediated MCs activation induced by LPS.
authors.affiliation: Department of Immunology and Pathogenic Biology, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an 710061, China; Department of Laboratory, The Second Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an 71004, China.
authors.forename: Li
authors.initials: L
authors.lastname: Xue
authors.affiliation: Department of Laboratory, The Second Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an 71004, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Geng
authors.affiliation: Department of Cardiovascular Surgery, The First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Pathology Department, The Second Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an 710004, China.
authors.forename: Yao-Feng
authors.initials: YF
authors.lastname: Jin
authors.affiliation: Department of Immunology and Pathogenic Biology, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an 710061, China.
authors.forename: Hui-Xun
authors.initials: HX
authors.lastname: Ren
authors.affiliation: VIP Internal Medicine Department, Lanzhou University Second Hospital, Lanzhou 730030, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.affiliation: Graduate Teaching and Experiment Centre, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an 710061, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wu
authors.affiliation: Department of Immunology and Pathogenic Biology, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an 710061, China.
authors.forename: Biao
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Immunology and Pathogenic Biology, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an 710061, China.
authors.forename: Wei-Ying
authors.initials: WY
authors.lastname: Cheng
authors.affiliation: Forensic Medicine College of Xi'an Jiaotong University, Key Laboratory of the Health Ministry for Forensic Medicine, Key Laboratory of the Ministry of Education for Environment and Genes Related to Diseases, Xi'an 710061, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Immunology and Pathogenic Biology, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an 710061, China. Electronic address: chenyanjiong@126.com.
authors.forename: Yan-Jiong
authors.initials: YJ
authors.lastname: Chen
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000502:physiology; D015550:Cell Degranulation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007155:Immunologic Factors / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000276:immunology; D008407:Mast Cells / Q000187:drug effects* / Q000502:physiology; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000235:genetics / Q000378:metabolism*; D017452:Receptors, IgG / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D016207:Cytokines; C485701:Fcgr1 protein, mouse; D007155:Immunologic Factors; D008070:Lipopolysaccharides; D016328:NF-kappa B; D050637:Receptors, Dopamine D3; D017452:Receptors, IgG; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D008694:Methamphetamine; D019009:Proto-Oncogene Proteins c-kit; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Dopamine D3 receptor; LPS; Mast cell activation; Methamphetamine