Role of сathepsin G in pathogenesis of chronic obstructive lung disease: possible ways of regulation

This review article presents the literature data supporting an idea on the role of serine proteases, and, especially, cathepsin G (CG), in pathogenesis of chronic obstructive pulmonary disease (COPD). Most studies show that the imbalance in protease-antiprotease systems in COPD is one of the main fa...

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Autores principales:	V. A. Beloglazov, I. A. Yatskov
Formato:	article
Lenguaje:	RU
Publicado:	SPb RAACI 2020
Materias:	сathepsin g copd proteases antiproteases phospholipid transfer proteins inhibitors Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/e976f6277941424da20b9abc391e8b21
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spelling	oai:doaj.org-article:e976f6277941424da20b9abc391e8b212021-11-18T08:03:49ZRole of сathepsin G in pathogenesis of chronic obstructive lung disease: possible ways of regulation1563-06252313-741X10.15789/1563-0625-ROC-1769https://doaj.org/article/e976f6277941424da20b9abc391e8b212020-05-01T00:00:00Zhttps://www.mimmun.ru/mimmun/article/view/1769https://doaj.org/toc/1563-0625https://doaj.org/toc/2313-741XThis review article presents the literature data supporting an idea on the role of serine proteases, and, especially, cathepsin G (CG), in pathogenesis of chronic obstructive pulmonary disease (COPD). Most studies show that the imbalance in protease-antiprotease systems in COPD is one of the main factors in the disease progression and deterioration of patient’s prognosis. CG seems to act simultaneously in several main pathogenetic aspects of the disease: it stimulates inflammation in the bronchial mucous membranes, leads to remodeling of elastic framework of the lungs, causes degradation of the phospholipid transfer protein (PLTP). A study by Gudmann et al. (2018) reported on quantitative assays of elastin fragments, which are formed under the action of CG (EL-CG) and significantly increased in COPD, thus proving the effects of CG on destruction of elastic framework in lungs. In a recent study, Rønnow S.R. et al. have recommended the assays of EL-CG fragments, reflecting elastin CG remodeling, for use as a prognostic biomarker for overall mortality in COPD. The effect of CG on PLTP was studied in the works of Brehm A. et al. It is known that the anti-inflammatory effect of PLTP is mediated by macrophages, via the ATP-binding cassette transporter (ABCA1), blocking the nuclear factor light chain enhancer (NF-kB) and reducing secretion of pro-inflammatory mediators by these cells, including (TNFα). The CG inhibition in bronchoalveolar lavage fluid (BALF) of the patients with COPD consistently disrupts its ability to cleave recombinant PLTP (rPLTP). At the same time, the highest CG activity was registered in BALF from smokers and in patients with COPD. Negative correlations between CG activity and PLTP level were detected. With respect to above, one may expect an increased interest for developing the inhibitors of serine proteases, including CG. E.g., the sunflower trypsin-1 inhibitor (SFTI-1) is a potent CG inhibitor, showing a significant increase of its activity when the P1 residue is replaced from Arg5 to Phe5. According to most researchers, powerful and selective CG inhibitors may be developed in future on the basis of SFTI-1, thus requiring further in-depth research.V. A. BeloglazovI. A. YatskovSPb RAACIarticleсathepsin gcopdproteasesantiproteasesphospholipid transfer proteinsinhibitorsImmunologic diseases. AllergyRC581-607RUMedicinskaâ Immunologiâ, Vol 22, Iss 3, Pp 443-448 (2020)
institution	DOAJ
collection	DOAJ
language	RU
topic	сathepsin g copd proteases antiproteases phospholipid transfer proteins inhibitors Immunologic diseases. Allergy RC581-607
spellingShingle	сathepsin g copd proteases antiproteases phospholipid transfer proteins inhibitors Immunologic diseases. Allergy RC581-607 V. A. Beloglazov I. A. Yatskov Role of сathepsin G in pathogenesis of chronic obstructive lung disease: possible ways of regulation
description	This review article presents the literature data supporting an idea on the role of serine proteases, and, especially, cathepsin G (CG), in pathogenesis of chronic obstructive pulmonary disease (COPD). Most studies show that the imbalance in protease-antiprotease systems in COPD is one of the main factors in the disease progression and deterioration of patient’s prognosis. CG seems to act simultaneously in several main pathogenetic aspects of the disease: it stimulates inflammation in the bronchial mucous membranes, leads to remodeling of elastic framework of the lungs, causes degradation of the phospholipid transfer protein (PLTP). A study by Gudmann et al. (2018) reported on quantitative assays of elastin fragments, which are formed under the action of CG (EL-CG) and significantly increased in COPD, thus proving the effects of CG on destruction of elastic framework in lungs. In a recent study, Rønnow S.R. et al. have recommended the assays of EL-CG fragments, reflecting elastin CG remodeling, for use as a prognostic biomarker for overall mortality in COPD. The effect of CG on PLTP was studied in the works of Brehm A. et al. It is known that the anti-inflammatory effect of PLTP is mediated by macrophages, via the ATP-binding cassette transporter (ABCA1), blocking the nuclear factor light chain enhancer (NF-kB) and reducing secretion of pro-inflammatory mediators by these cells, including (TNFα). The CG inhibition in bronchoalveolar lavage fluid (BALF) of the patients with COPD consistently disrupts its ability to cleave recombinant PLTP (rPLTP). At the same time, the highest CG activity was registered in BALF from smokers and in patients with COPD. Negative correlations between CG activity and PLTP level were detected. With respect to above, one may expect an increased interest for developing the inhibitors of serine proteases, including CG. E.g., the sunflower trypsin-1 inhibitor (SFTI-1) is a potent CG inhibitor, showing a significant increase of its activity when the P1 residue is replaced from Arg5 to Phe5. According to most researchers, powerful and selective CG inhibitors may be developed in future on the basis of SFTI-1, thus requiring further in-depth research.
format	article
author	V. A. Beloglazov I. A. Yatskov
author_facet	V. A. Beloglazov I. A. Yatskov
author_sort	V. A. Beloglazov
title	Role of сathepsin G in pathogenesis of chronic obstructive lung disease: possible ways of regulation
title_short	Role of сathepsin G in pathogenesis of chronic obstructive lung disease: possible ways of regulation
title_full	Role of сathepsin G in pathogenesis of chronic obstructive lung disease: possible ways of regulation
title_fullStr	Role of сathepsin G in pathogenesis of chronic obstructive lung disease: possible ways of regulation
title_full_unstemmed	Role of сathepsin G in pathogenesis of chronic obstructive lung disease: possible ways of regulation
title_sort	role of сathepsin g in pathogenesis of chronic obstructive lung disease: possible ways of regulation
publisher	SPb RAACI
publishDate	2020
url	https://doaj.org/article/e976f6277941424da20b9abc391e8b21
work_keys_str_mv	AT vabeloglazov roleofsathepsinginpathogenesisofchronicobstructivelungdiseasepossiblewaysofregulation AT iayatskov roleofsathepsinginpathogenesisofchronicobstructivelungdiseasepossiblewaysofregulation
_version_	1718422323810271232

Role of сathepsin G in pathogenesis of chronic obstructive lung disease: possible ways of regulation

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