Background: Chitinases are a family of hydrolases characterized by the ability to cleave the environmental polysaccharide chitin. Although mammals do not synthesize chitin, they do synthesize chitinases, and chitinase-like proteins (CLPs). The physiological and biological role of these secretory proteins remains unclear. However, recent studies conducted in arthritis, asthma, inflammatory bowel diseases and cancer suggest chitinases and CPLs play an important role in inflammatory processes and tissue remodeling. Objective: To investigate the role of chitinases and CPLs in Multiple Sclerosis (MS) and Neuromyelitis optica (NMO) Methods: Levels of chitotriosidase, acidic mammalian chitinase (AMCase), and chitinase 3-like 1 (CHI3L1), were studied using ELISA in CSF and serum from 24 patients with relapsing remitting (RR) MS, 24 patients with secondary progressive (SP) MS, 12 NMO patients, and 24 healthy age- and gender-matched controls (HCs). Numbers of anti-MOG IL-5, IL-6, and IL-13 secreting cells in PBMC and CSF were studied using ELISPOT. Eotaxin-2 (EO-2), Eotaxin-3 (Eo-3), MCP, RANTES and IL-8 were also assessed using ELISA. Results: CSF levels of chitinases were significantly higher in RR MS and NMO patients compared to SP MS patients and HCs (p= 0.001 and p less than 0.0001). Moreover, CSF levels of all 3 chitinases were significantly higher in NMO patients compared to the three control populations (p less than 0.0001). No significant differences were detected in chitinase serum levels between the four groups studied. In CSF from NMO patients, a robust correlation was observed between chitinase levels and number of anti-MOG IL-13 producing cells (r= 0.81; p =0.01), as well as levels of Eo-2, and Eo-3 (r= 0.65; p= 0.02). In vitro experiments showed secretion of AMCase and chitotriosidase was significantly increased by IL-13, but not by IL-5 or IL-6. Moreover, chitinases activated NF-kappaB transcription and enhanced IL-8, RANTES, MCP-1, Eo-2 and Eo3 production. These effects were abrogated using the pan-chitinase inhibitor Allosamidine or specific simRNA. Conclusions: These observations suggest chitinases are increased in CSF from NMO patients in response to IL-13. We believe these enhanced chitinases levels may contribute to tissue inflammation through increased eosinophil, T cell and macrophage migration.
Read More: The role of chitinases in multiple sclerosis and neuromyelitis optica