title: Chitinase effects on immune cell response in neuromyelitis optica and multiple sclerosis.
abstract: BACKGROUND
  Recent studies conducted in arthritis, asthma, and inflammatory bowel disease suggest that chitinases are important in inflammatory processes and tissue remodeling.
  
  
  OBJECTIVE
  To investigate the role of chitinases in multiple sclerosis (MS) and neuromyelitis optica (NMO).
  
  
  METHODS
  Levels of chitotriosidase, acid mammalian chitinase (AMCase), and chitinase 3-like-1 (CHI3L1) were measured using ELISA, in cerebrospinal fluid (CSF) and in serum from 24 patients with relapsing remitting (RR) MS, 24 patients with secondary progressive (SP) MS, 12 patients with NMO, 24 patients with other inflammatory neurological diseases (OIND), and 24 healthy controls (HCs). The number of anti-MOG cytokine-secreting cells was studied using ELISPOT. Eotaxins, MCP-1, RANTES, and IL-8 were assessed using ELISA. Cell transmigration was determined using an in vitro blood-brain barrier (BBB) model, in the presence and absence of chitinases.
  
  
  RESULTS
  CSF chitinase levels were significantly increased in patients with RRMS and NMO compared with HCs and patients with SPMS and OIND. In contrast, no significant differences were detected in serum chitinase levels between groups. Chitinase CSF levels showed correlation with anti-MOG IL-13-producing cells, and eotaxin levels. In vitro experiments showed macrophage chitinase secretion was significantly increased by IL-13, but not by IL-5, IL-6, IL-12, or IFN-γ. Moreover, chitinases enhanced IL-8, RANTES, MCP-1, and eotaxin production, increasing migratory capacity in eosinophils, T cells, and macrophages across an in vitro BBB model.
  
  
  CONCLUSIONS
  Chitinases increased in the CSF from patients with NMO in response to IL-13. These enhanced levels could contribute to central nervous system inflammation by increasing immune cell migration across the BBB.
authors.affiliation: Department of Neurology, Raúl Carrea Institute for Neurological Research, FLENI, Buenos Aires, Argentina. jcorreale@fleni.org.ar
authors.forename: Jorge
authors.initials: J
authors.lastname: Correale
authors.forename: Marcela
authors.initials: M
authors.lastname: Fiol
mesh_terms: D054392:Adipokines; D000328:Adult; D001118:Argentina; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D001812:Blood-Brain Barrier / Q000201:enzymology / Q000276:immunology; D016022:Case-Control Studies; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D000071451:Chitinase-3-Like Protein 1; D002688:Chitinases / Q000097:blood / Q000134:cerebrospinal fluid; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D042783:Endothelial Cells / Q000201:enzymology / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D006023:Glycoproteins / Q000097:blood / Q000134:cerebrospinal fluid; D006596:Hexosaminidases / Q000097:blood / Q000134:cerebrospinal fluid; D006801:Humans; D037102:Lectins / Q000097:blood / Q000134:cerebrospinal fluid; D007963:Leukocytes, Mononuclear / Q000201:enzymology* / Q000276:immunology; D008297:Male; D020528:Multiple Sclerosis, Chronic Progressive / Q000097:blood / Q000134:cerebrospinal fluid / Q000201:enzymology* / Q000276:immunology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000134:cerebrospinal fluid / Q000201:enzymology* / Q000276:immunology; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D009471:Neuromyelitis Optica / Q000097:blood / Q000134:cerebrospinal fluid / Q000201:enzymology* / Q000276:immunology; D057705:Transendothelial and Transepithelial Migration; D015854:Up-Regulation
chemical_list: D054392:Adipokines; D015415:Biomarkers; C084533:CHI3L1 protein, human; D018925:Chemokines; D000071451:Chitinase-3-Like Protein 1; D016207:Cytokines; D006023:Glycoproteins; D037102:Lectins; C571326:MOG protein, human; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D006596:Hexosaminidases; C086400:chitotriosidase; C499254:CHIA protein, human; D002688:Chitinases