Elevated IL-33 promotes expression of MMP2 and MMP9 via activating STAT3 in alveolar macrophages during LPS-induced acute lung injury

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background

Pulmonary inflammation and endothelial barrier permeability increase in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) induced by pro-inflammatory cytokines and matrix metalloproteinases (MMPs). However, the relationship between pro-inflammatory cytokines and MMPs in ALI/ARDS remains poorly understood.

Methods

A lipopolysaccharide (LPS)-induced ALI rat model was established through intratracheal instillation. The wet/dry ratios of lung tissues were measured, and bronchoalveolar lavage fluid (BALF) was collected to test protein concentrations, total cell/macrophage numbers, and pro-inflammatory cytokine levels. LPS-treated alveolar macrophages were utilized in in vitro experiments. The expression and secretion of MMPs were respectively detected using quantitative PCR, Western blotting and ELISA assays.

Results

The levels of IL-33 and MMP2/9 in BALF increased in all the ALI rats with severe lung injury. LPS-induced IL-33 autocrine upregulated the expression of MMP2 and MMP9 through activating STAT3. Neutralizing IL-33 in culture medium with specific antibodies suppressed the expression and secretion of MMP2 and MMP9 in LPS-treated alveolar macrophages. Consistently, eliminating IL-33 decreased the levels of MMP2 and MMP9 in BALF and alleviated lung injury in ALI rats.

Conclusion

The IL-33/STAT3/MMP2/9 regulatory pathway is activated in alveolar macrophages during acute lung injury, which may exacerbate the pulmonary inflammation.

Related collections

Most cited references 19

Record: found
Abstract: found
Article: not found

Matrix metalloproteinases in acute lung injury: mediators of injury and drivers of repair.

Robert Davey, C J O'Kane, D McAuley (2011)

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) comprise a spectrum of acute inflammatory pulmonary oedema resulting in refractory hypoxaemia in the absence of an underlying cardiogenic cause. There are multiple pulmonary and extrapulmonary causes and ALI/ARDS patients are a clinically heterogeneous group with associated high morbidity and mortality. Inflammatory injury to the alveolar epithelial and endothelial capillary membrane is a central event in the pathogenesis of ALI/ARDS, and involves degradation of the basement membrane. Matrix metalloproteinases (MMPs) have been implicated in a wide variety of pulmonary pathologies and are capable of degrading all components of the extracellular matrix including the basement membrane and key non-matrix mediators of lung injury such as chemokines and cell surface receptors. While many studies implicate MMPs in the injurious process, there are significant gaps in our knowledge of the role of specific proteases at different phases of injury and repair. This article examines the role of MMPs in injury and repair of the alveolar epithelial-endothelial capillary barrier and discusses the potential for MMP modulation in the prevention and treatment of ALI. The need for further mechanistic and in vivo studies to inform appropriate subsequent clinical trials of MMP modulation will be highlighted.

0 comments Cited 97 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

Acute respiratory distress syndrome

Marco Confalonieri, Francesco Salton, Francesco Fabiano (2017)

Since its first description, the acute respiratory distress syndrome (ARDS) has been acknowledged to be a major clinical problem in respiratory medicine. From July 2015 to July 2016 almost 300 indexed articles were published on ARDS. This review summarises only eight of them as an arbitrary overview of clinical relevance: definition and epidemiology, risk factors, prevention and treatment. A strict application of definition criteria is crucial, but the diverse resource-setting scenarios foster geographic variability and contrasting outcome data. A large international multicentre prospective cohort study including 50 countries across five continents reported that ARDS is underdiagnosed, and there is potential for improvement in its management. Furthermore, epidemiological data from low-income countries suggest that a revision of the current definition of ARDS is needed in order to improve its recognition and global clinical outcome. In addition to the well-known risk-factors for ARDS, exposure to high ozone levels and low vitamin D plasma concentrations were found to be predisposing circumstances. Drug-based preventive strategies remain a major challenge, since two recent trials on aspirin and statins failed to reduce the incidence in at-risk patients. A new disease-modifying therapy is awaited: some recent studies promised to improve the prognosis of ARDS, but mortality and disabling complications are still high in survivors in intensive care. A review of acute respiratory distress syndrome http://ow.ly/ITXq308ZLtE

0 comments Cited 81 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Mechanisms and clinical consequences of acute lung injury.

Vito Fanelli, V Ranieri (2015)

Acute respiratory distress syndrome (ARDS) was first described in 1967, and since then there have been a large number of studies addressing its pathogenesis and therapies. Despite intense research efforts, very few therapies for ARDS have been shown to be effective other than the use of lung protection strategies. The scarcity of therapeutic choices is related to the intricate pathogenesis of the syndrome and to insensitive and aspecific criteria to diagnose this profound acute respiratory failure. The aim of this paper is to summarize advances of new ARDS definitions and provide an overview of new relevant signaling pathways that mediate acute lung injury.

0 comments Cited 65 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Yafeng Liang: lyafeng77@163.com

Nengli Yang: ynengli@163.com

Guoquan Pan: 818001800@163.com

Bingxin Jin: 371272030@qq.com

Shufen Wang: 2644373031@qq.com

Wei Ji: +86-13962108901 , szdxjiwei@163.com

Journal

Journal ID (nlm-ta): Cell Mol Biol Lett

Journal ID (iso-abbrev): Cell. Mol. Biol. Lett

Title: Cellular & Molecular Biology Letters

Publisher: BioMed Central (London )

ISSN (Print): 1425-8153

ISSN (Electronic): 1689-1392

Publication date (Electronic): 31 October 2018

Publication date PMC-release: 31 October 2018

Publication date Collection: 2018

Volume: 23

Electronic Location Identifier: 52

Affiliations

[1 ]GRID grid.452253.7, Department of Pediatric Pulmonology, , Children’s Hospital of Soochow University, ; No 303, Jingde Road, Suzhou, 215003 China

[2 ]ISNI 0000 0001 0348 3990, GRID grid.268099.c, Department of Pediatric Intensive Care Unit, The Second Affiliated Hospital & Yuying Children’s Hospital, , Wenzhou Medical University, ; Wenzhou, 325000 China

[3 ]ISNI 0000 0004 1808 0918, GRID grid.414906.e, Department of Anesthesiology, , The First Affiliated Hospital of Wenzhou Medical University, ; Wenzhou, 325000 China

Article

Publisher ID: 117

DOI: 10.1186/s11658-018-0117-x

PMC ID: 6208075

PubMed ID: 30410547

SO-VID: e0e9fb93-95a2-49d9-bcfb-8b58942c2d81

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 20 June 2018

Date accepted : 12 October 2018

Funding

Funded by: Zhejiang Provincial Natural Science Foundation

Award ID: LY17H150004

Award Recipient : Yafeng Liang

Funded by: Medicine and Health Science and Technology projects of Zhejiang Province

Award ID: 2018KY528

Award ID: 2017KY478

Award Recipient : Yafeng Liang Guoquan Pan

Custom metadata

Keywords: acute lung injury (ali),il-33,mmp2,mmp9,stat3

Data availability:

Keywords: acute lung injury (ali), il-33, mmp2, mmp9, stat3

Comments

Comment on this article

scite_

Cited by 38

See all cited by

Most referenced authors 230

See all reference authors

Elevated IL-33 promotes expression of MMP2 and MMP9 via activating STAT3 in alveolar macrophages during LPS-induced acute lung injury

Read this article at

Abstract

Background

Methods

Results

Conclusion

Related collections

In vitro alveolar region models

Most cited references 19

Matrix metalloproteinases in acute lung injury: mediators of injury and drivers of repair.

Acute respiratory distress syndrome

Mechanisms and clinical consequences of acute lung injury.

Author and article information

Contributors

Journal

Affiliations

Article

History

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 220

Cited by 38

Most referenced authors 230