title: Macrophage migration inhibitory factor activates inflammatory responses of astrocytes through interaction with CD74 receptor.
abstract: Astrocytes, the major glial cell population of the central nervous system (CNS), play important physiological roles related to CNS homeostasis. Growing evidence demonstrates that astrocytes trigger innate immune responses under challenge of a variety of proinflammatory cytokines. Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine mainly secreted from monocytes/macrophages, is involved in inflammation-associated pathophysiology. Here, we displayed that expression of MIF significantly increased following spinal cord injury, in colocalization with microglia and astrocytes. MIF elicited inflammatory responses of astrocytes via activation of CD74 receptor and extracellular signal-related kinase (ERK) pathway. Transcriptome analysis revealed that inflammation-related factors cholesterol 25-hydroxylase (Ch25h) and phospholipase A2-IIA (Pla2g2a), downstream of MIF/CD74 axis, were potentially implicated in the mediating inflammatory response of astrocytes. Our results provided a new target for interference of CNS inflammation after insults.
authors.affiliation: Key Laboratory of Neuroregeneration, Ministry of Education and Jiangsu Province, Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Su
authors.affiliation: Key Laboratory of Neuroregeneration, Ministry of Education and Jiangsu Province, Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, PR China.
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Rehabilitation Medicine, Affiliated Hospital of Nantong University, Nantong 226001, PR China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Rehabilitation Medicine, Affiliated Hospital of Nantong University, Nantong 226001, PR China.
authors.forename: Zhenjie
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Neuroregeneration, Ministry of Education and Jiangsu Province, Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, PR China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Neuroregeneration, Ministry of Education and Jiangsu Province, Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, PR China.
authors.forename: Xuejie
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Neuroregeneration, Ministry of Education and Jiangsu Province, Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, PR China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Wang
authors.affiliation: Key Laboratory of Neuroregeneration, Ministry of Education and Jiangsu Province, Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, PR China.
authors.forename: Xiaosong
authors.initials: X
authors.lastname: Gu
authors.affiliation: Department of Rehabilitation Medicine, Affiliated Hospital of Nantong University, Nantong 226001, PR China.
authors.forename: Aisong
authors.initials: A
authors.lastname: Guo
authors.affiliation: Key Laboratory of Neuroregeneration, Ministry of Education and Jiangsu Province, Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, PR China.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics / Q000378:metabolism*; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D015415:Biomarkers; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D053263:Gene Regulatory Networks; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism*; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D011485:Protein Binding; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000209:etiology / Q000378:metabolism / Q000473:pathology
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D015415:Biomarkers; D000949:Histocompatibility Antigens Class II; D008263:Macrophage Migration-Inhibitory Factors; C045084:invariant chain; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: CD74; MIF; astrocyte; inflammation; spinal cord