Allergy Asthma Immunol Res.  2015 Jan;7(1):14-21. 10.4168/aair.2015.7.1.14.

Chitotriosidase in the Pathogenesis of Inflammation, Interstitial Lung Diseases and COPD

• Cho SJ
• Weiden MD
• Lee CG

• KMID: 2260147
• DOI: http://doi.org/10.4168/aair.2015.7.1.14

Abstract

As a member of 18 glycosyl hydrolase (GH) family, chitotriosidase (Chitinase 1, CHIT1) is a true chitinase mainly expressed in the differentiated and polarized macrophages. CHIT1 is an innate immune mediator that digests the cell walls of chitin-containing eukaryotic pathogens, such as fungi. However, CHIT1 is dysregulated in granulomatous and fibrotic interstitial lung diseases characterized by inflammation and tissue remodeling. These include tuberclosis, sarcoidosis, idiopathic pulmonary fibrosis, scleroderma-associated interstitial lung diseases (SSc-ILD), and chronic obstructive lung diseases (COPD). CHIT1 serum concentration correlates with the progression or the severity of these diseases, suggesting a potential use of CHIT1 as a biomarker or a therapeutic target. Recent studies with genetically modified mice demonstrate that CHIT1 enhances TGF-beta1 receptor expression and signaling, suggesting a role in initiating or amplifying the response to organ injury and repair. This additional CHIT1 activity is independent of its enzymatic activity. These studies suggest that CHIT1 serves a bridging function; it is both an innate immune mediator and a regulator of tissue remodeling. This review will focus on recent data linking CHIT1 to the pathogenesis of inflammation, interstitial lung disease, and COPD.

Keyword

Chitotriosidase; sarcoidosis; scleroderma; idiopathic pulmonary fibrosis; inflammation; TGF-beta

MeSH Terms

Animals
Cell Wall
Chitinase
Fungi
Humans
Idiopathic Pulmonary Fibrosis
Inflammation*
Lung Diseases, Interstitial*
Lung Diseases, Obstructive
Macrophages
Mice
Pulmonary Disease, Chronic Obstructive*
Sarcoidosis
Transforming Growth Factor beta
Transforming Growth Factor beta1
Chitinase
Transforming Growth Factor beta
Transforming Growth Factor beta1

Figure

• 

  Figure Schematic illustration on chitotriosidase (CHIT1) regulation of TGF-β pathway. CHIT1 enhances the effect of TGF-β through the induction of TGF-β receptors expression (both type I and type II) and TGF-β signaling. In the preliminary studies in our laboratory suggest that CHIT1 could bind with a transcription factor such as FoxO3a, or TGF-β receptor associated protein 1 (TGFBRAP1) (unpublished data), modulates TGF-β-stimulated canonical (Smads-dependent) and/or non-canonical MAPK/Erk or Akt signaling. Erk or Akt activation generally increases cell survival or proliferation, that might contribute to the development of tissue fibrosis together with increased expression of profibrotic mediators and extracellular matrix protein accumulation. The exact role and mechanism of CHIT1 in this regulation (such as receptor or interacting proteins of CHIT1) need to be determined in future studies.

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