Chitinases and chitinase-like proteins: potential therapeutic targets for the treatment of T-helper type 2 allergies.
Mammalian chitinase and chitinase-like proteins (CLPs) are a family of mediators increasingly associated with infection, T cell-mediated inflammation, wound healing, allergy and asthma. Although our current knowledge of the function of mammalian chitinases and CLPs is very limited, important information can be deduced from research carried out in lower organisms, and in different immunopathological conditions. Enzymatically active mammalian chitinase proteins may have evolved to degrade the copious amounts of chitin mammals are exposed to on a daily basis, and to form an innate barrier to chitin-containing organisms. CLPs are homologous to chitinases but lack the ability to degrade chitin. It is most striking that both chitinases and CLPs are up-regulated in T-helper type 2 (Th2)-driven conditions, and the first evidence is now emerging that these proteins may accentuate Th2 reactivity, and possibly contribute to the repair process that follows inflammation. Following studies demonstrating that chitinase inhibition leads to an attenuated allergic response, several strategies are being used to develop enzyme inhibitors for therapeutic use in human diseases. In this review, we will summarize recent insights into the effects of chitinases and CLPs in the context of Th2-dominated pathology with particular focus on allergy and asthma, discussing whether chitinase enzyme inhibitors may be of therapeutic value.
Sutherland
T E
TE
Ashworth Laboratories, Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, UK. tara.sutherland@ed.ac.uk
Maizels
R M
RM
Allen
J E
JE
D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000201:enzymology / Q000276:immunology; D002688:Chitinases / Q000037:antagonists & inhibitors* / Q000276:immunology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology; D018418:Th2 Cells / Q000201:enzymology* / Q000276:immunology*
D004791:Enzyme Inhibitors; D002688:Chitinases