Role of mammalian chitinases in inflammatory conditions.

Abstract

It has been hypothesized that dysregulated host/microbial interactions play a pivotal role in the pathogenesis of inflammatory bowel disease. However, the exact mechanisms underlying the induction and perpetuation of the intestinal disorder are unclear. Recently, we unexpectedly discovered significantly upregulated gene expression of chitinase 3-like-1 in inflamed colon of the dextran sulfate sodium-induced colitis model by employing the DNA-microarray analysis. Chitinase 3-like-1 has a chitin binding ability, but lacks the enzymatic activity of lysing microbial cell wall. Chitinase 3-like-1 protein is mainly expressed in colonic epithelial cells and macrophages in the inflamed colon of dextran sulfate sodium-induced colitis. Chitinase 3-like-1, which can be upregulated after pro-inflammatory cytokine stimulation, possesses an ability to enhance the adhesion and internalization of intracellular bacteria into colonic epithelial cells. Most importantly, in vivo neutralization of chitinase 3-like-1 significantly suppressed the development of dextran sulfate sodium-induced colitis by dramatically decreasing the bacterial adhesion and invasion into colonic epithelial cells. Furthermore, anti-chitinase 3-like-1 antibody-treated mice exhibited a significantly lower load of Salmonella typhimurium in peripheral organs as compared to control rabbit IgG-treated mice. Recently, it has been reported that acidic mammalian chitinase is expressed in the setting of T helper-2-associated inflammation and subsequently induces airway hyperresponsiveness in allergic asthma patients. In addition, pan-chitinase inhibitor significantly ameliorates T helper-2-mediated inflammation and airway hypersensitivity. These studies provide to be a novel insight into the physiological role of mammalian chitinases in host/microbial interactions, and inhibition of chitinase activity would be considered a novel therapeutic strategy of allergic and inflammatory disorders.

• Authors: Mayumi Kawada, Yuriko Hachiya, Atsuko Arihiro, Emiko Mizoguchi
• Journal: The Keio journal of medicine (Keio J Med) Vol. 56 Issue 1 Pg. 21-7 (Mar 2007) ISSN: 0022-9717 [Print] Japan
• PMID: 17392594 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Adipokines
• Bacterial Proteins
• CHI3L1 protein, human
• Carrier Proteins
• Chitinase-3-Like Protein 1
• Enzyme Inhibitors
• Glycoproteins
• Intracellular Signaling Peptides and Proteins
• Lectins
• chitin-binding protein 21, Serratia marcescens
• CHIA protein, human
• Chitinases

Topics

• Adipokines
• Animals
• Bacterial Proteins (physiology)
• Carrier Proteins (physiology)
• Chitinase-3-Like Protein 1
• Chitinases (antagonists & inhibitors, physiology)
• Enzyme Inhibitors (therapeutic use)
• Glycoproteins (physiology)
• Humans
• Inflammation (etiology)
• Inflammatory Bowel Diseases (etiology)
• Intracellular Signaling Peptides and Proteins
• Lectins