title: Ulinastatin attenuates experimental autoimmune encephalomyelitis by enhancing anti-inflammatory responses.
abstract: Multiple sclerosis (MS) is a common inflammatory and demyelinating neurological disease. Experimental autoimmune encephalomyelitis (EAE), an animal model of MS, has been widely used to test MS treatment methods. Ulinastatin (UTI), a drug used to treat acute inflammatory disorders, has been tested in animal models of autoimmune inflammatory diseases, such as ulcerative colitis and crescentic glomerulonephritis. We recently found that UTI has a neuroprotective effect on EAE by reducing oligodendrocyte apoptosis and demyelination. The anti-inflammatory effects of UTI on EAE/MS, however, have never been investigated. We have therefore evaluated the anti-inflammatory effects of UTI in EAE and explored the mechanisms underlying this effect. EAE was induced in mice with and without UTI treatment. Inflammation and demyelination of spinal cords were evaluated by staining with hematoxylin and eosin and with Luxol fast blue, respectively. Inflammatory markers in serum were analyzed by the Luminex method, and spinal cords were evaluated by immunofluorescence and Western blotting. UTI significantly lowered the clinical and pathological scores and the serum concentrations of the inflammatory cytokines interleukin (IL)-1β, IL-6, and matrix metal protease-9 (MMP-9). UTI also reduced the expression of tumor necrosis factor-alpha (TNF-α)/nuclear factor kappaB (NF-κB)/inducible nitric oxide synthase (iNOS) proteins and decreased CD11b(+) cells in spinal cord lesions. UTI may protect against EAE in mice by suppressing inflammatory responses. We think that UTI might be a potential therapeutic agent for MS.
authors.affiliation: Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China; Department of Gerontology and Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Feng
authors.affiliation: Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China.
authors.forename: Yaqing
authors.initials: Y
authors.lastname: Shu
authors.affiliation: Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Neurology, The Affiliated Hospital of Qingdao Medical College, Qingdao University, Qingdao 266003, China.
authors.forename: Xueping
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China.
authors.forename: Yuge
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China.
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Dai
authors.affiliation: Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Qiu
authors.affiliation: Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China.
authors.forename: Zhengqi
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China. Electronic address: huxueqiangzssy@qq.com.
authors.forename: Xueqiang
authors.initials: X
authors.lastname: Hu
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D005260:Female; D006023:Glycoproteins / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D004676:Myelin Basic Protein / Q000378:metabolism; D013116:Spinal Cord / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*
chemical_list: D016207:Cytokines; D006023:Glycoproteins; D015850:Interleukin-6; D004676:Myelin Basic Protein; D014409:Tumor Necrosis Factor-alpha; C028665:urinastatin
keywords: BDNF; CNS; EAE; Experimental autoimmune encephalomyelitis; HE; IF; IFN-γ; Inflammatory responses; LFB; Luxol fast blue; MCP-1; MIP-2; MMP-9; MS; NF-κB; NGF; RANTES; TNF-α; UTI; Ulinastatin; brain-derived neurotrophic factor; central nervous system; experimental autoimmune encephalomyelitis; hematoxylin and eosin; iNOS; immunofluorescence; inducible nitric oxide synthase; interferon-γ; macrophage inflammatory protein-2; matrix metalloproteinase-9; monocyte chemotactic protein-1; multiple sclerosis; nerve growth factor; nuclear factor kappaB; regulated upon activation normal T cell expressed and presumably secreted; sICAM-1; soluble intercellular adhesion molecule-1; tumor necrosis factor-alpha; ulinastatin