Role of ADAM and ADAMTS metalloproteinases in airway diseases

Genevieve Paulissen,Celine Crahay,Jonathan Hacha,Natacha Rocks,Didier D Cataldo,Sandrine Bekaert,Jean-Michel Foidart,Florence Quesada-Calvo,Maud M Gueders,Mehdi El Hour,Agnes Noel

doi:10.1186/1465-9921-10-127

Abstract

Lungs are exposed to the outside environment and therefore to toxic and infectious agents or allergens. This may lead to permanent activation of innate immune response elements. A Disintegrin And Metalloproteinases (ADAMs) and ADAMs with Thrombospondin motifs (ADAMTS) are proteinases closely related to Matrix Metalloproteinases (MMPs). These multifaceted molecules bear metalloproteinase and disintegrin domains endowing them with features of both proteinases and adhesion molecules. Proteinases of the ADAM family are associated to various physiological and pathological processes and display a wide spectrum of biological effects encompassing cell fusion, cell adhesion, "shedding process", cleavage of various substrates from the extracellular matrix, growth factors or cytokines... This review will focus on the putative roles of ADAM/ADAMTS proteinases in airway diseases such as asthma and COPD.

Highlights

The lung is continuously exposed to the outside environment and various potential aggressions such as noxious and infectious agents or allergens
The present review focuses on another subfamily of proteinases belonging to the metzincins and structurally related to Matrix Metalloproteinases (MMPs): the A Disintegrin And Metalloproteinases (ADAMs) (A Disintegrin And Metalloproteinase) [10,11,12,13,14]
Despite the improvement of therapeutic strategies and a better understanding of this disease, the morbidity and mortality related to Chronic obstructive pulmonary disease (COPD) are still significant. Matrix metalloproteinases such as MMP-9 and MMP-12 which have been reported to be modulated in airway secretions from COPD patients might contribute to disease progression and exacerbations by their catalytic activity

Summary

Introduction

The lung is continuously exposed to the outside environment and various potential aggressions such as noxious and infectious agents or allergens. When taking into consideration the complex multidomain structure of ADAMs and ADAMTS, one can anticipate their implication in many physiological and pathological processes From these complex structural features and bearing in mind that only half of proteins of this family display a catalytic activity, one can expect that functions of ADAMs and ADAMTS will not be restricted to the http://respiratory-research.com/content/10/1/127 cleavage of extracellular matrix or mediators but will embrace various functions including the regulation of cell-cell and cell-matrix interactions. Matrix metalloproteinases such as MMP-9 and MMP-12 which have been reported to be modulated in airway secretions from COPD patients might contribute to disease progression and exacerbations by their catalytic activity Despite their potential importance in this disease, only few data are available concerning ADAM proteinases involvement in COPD (see figure 2). SiRNA (small interfering RNA) raised against ADAM-17 mRNA as well as metalloproteinase inhibitors (GM-6001 and TNF-alpha inhibitor 1), prevent smoking- induced mucin overproduction in human airway epithelial cells (NCI-H292 cells) [81]

Conclusions

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