ADAM8: a new therapeutic target for asthma

Expert Opin Ther Targets. 2009 May;13(5):523-40. doi: 10.1517/14728220902889788.

Abstract

Background: A proteinase with a disintegrin and a metalloproteinase domain-8 (ADAM8) has been linked to asthma.

Objective: To explore whether ADAM8 is a therapeutic target for asthma.

Methods: We reviewed literature on ADAM8's function and expression and activities in lungs of humans and mice with allergic airway inflammation (AAI). We used these data to generate hypotheses about the contributions of ADAM8 to asthma pathogenesis.

Conclusions: ADAM8 levels are increased in airway epithelium and airway inflammatory cells in mice with AAI and human asthma patients. Data from murine models of AAI indicate that ADAM8 dampens airway inflammation. It is not clear whether ADAM8 contributes directly to structural remodeling in asthmatic airways. Additional studies are required to validate ADAM8 as a therapeutic target for asthma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ADAM Proteins / antagonists & inhibitors*
  • ADAM Proteins / chemistry
  • ADAM Proteins / deficiency
  • ADAM Proteins / physiology
  • Animals
  • Anti-Asthmatic Agents / pharmacology*
  • Anti-Asthmatic Agents / therapeutic use
  • Antigens, CD
  • Asthma / drug therapy*
  • Asthma / enzymology
  • Asthma / immunology
  • Asthma / pathology
  • Child
  • Cytokines / metabolism
  • Drug Delivery Systems*
  • Drug Evaluation, Preclinical
  • Epithelial Cells / enzymology
  • Extracellular Matrix Proteins / metabolism
  • Fibrosis
  • Humans
  • Leukocytes / enzymology
  • Lung / enzymology
  • Lung / pathology
  • Membrane Proteins / antagonists & inhibitors*
  • Membrane Proteins / chemistry
  • Membrane Proteins / deficiency
  • Membrane Proteins / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Protease Inhibitors / pharmacology*
  • Protease Inhibitors / therapeutic use
  • Protein Structure, Tertiary
  • Pulmonary Eosinophilia / drug therapy
  • Pulmonary Eosinophilia / enzymology
  • Pulmonary Eosinophilia / etiology
  • Receptors, Cell Surface / metabolism

Substances

  • Anti-Asthmatic Agents
  • Antigens, CD
  • Cytokines
  • Extracellular Matrix Proteins
  • Membrane Proteins
  • Protease Inhibitors
  • Receptors, Cell Surface
  • ADAM Proteins
  • ADAM8 protein, human
  • Adam8 protein, mouse