24. Proteases in Allergy

  1. Kenji Izuhara MD, PhD2,
  2. Stephen T. Holgate MD, DSc, FMedSci3 and
  3. Marsha Wills-Karp PhD4
  1. Keisuke Oboki PhD and
  2. Hirohisa Saito MD, PhD

Published Online: 27 JUL 2011

DOI: 10.1002/9781444346688.ch24

Inflammation and Allergy Drug Design

Inflammation and Allergy Drug Design

How to Cite

Oboki, K. and Saito, H. (2011) Proteases in Allergy, in Inflammation and Allergy Drug Design (eds K. Izuhara, S. T. Holgate and M. Wills-Karp), Wiley-Blackwell, Oxford, UK. doi: 10.1002/9781444346688.ch24

Editor Information

  1. 2

    Department of Biomolecular Sciences, Division of Medical Biochemistry, Saga Medical School, Nabeshima, Saga, Japan

  2. 3

    School of Medicine, Allergy and Inflammation Research, Southampton General Hospital, University Medicine, Southampton, UK

  3. 4

    Division of Immunology, Cincinnati Children's Medical Center, Cincinnati, OH, USA

Author Information

  1. Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo, Japan

Publication History

  1. Published Online: 27 JUL 2011
  2. Published Print: 13 AUG 2011

ISBN Information

Print ISBN: 9781444330144

Online ISBN: 9781444346688



  • proteases in allergy;
  • inflammasome, identified - as a molecular complex activation of inflammatory caspases;
  • endogenous proteases, mast cell role - in bronchial asthma, airway inflammation;
  • patients with asthma, accelerated loss of lung function - and fixed airflow obstruction;
  • cytokines, mediating late-phase reaction - inflammatory infiltrate of eosinophils, basophils, neutrophils and lymphocytes;
  • conservation and evolution - of mast cell proteases, expressing carboxypeptidase A3/mast cell carboxypeptidase A (MC-CPA);
  • exogenous proteases - and house dust mite proteases, Dermatophagoides farinae and Dermatophagoides pteronyssinus;
  • activation of innate pattern recognition receptors - as toll-like receptors (TLRs), in helper T type 1 cell differentiation;
  • role of proteases in allergic inflammation - in airways, Der p1 allergen inhaled;
  • pathologies, and asthma, atopic dermatitis - other allergic diseases, abnormal activities of endo- and exogenous proteases


The roles of endogenous proteases, such as mast cell tryptase, and exogenous proteases, such as house dust mite (HDM) allergens in asthma and allergic diseases, are discussed in this chapter. Mast cell neutral proteases such as tryptase are the dominant protein components in the secretory granules. Tryptase is involved in the proliferation of airway smooth muscle cells, an essential element of irreversible airway narrowing in severe asthmatics, probably via proteolysis of other growth factors on airway smooth muscle cells. HDM is a major source of allergens associated with allergic diseases. The group 1 HDM major allergens belong to papain-like cyteine protease family and facilitate transepithelial allergen delivery by disruption of tight junctions of bronchial epithelium. HDM or papain triggers Toll-like receptor 4, which is present on the airway structural cells or basophils to produce the proallergic cytokines such as thymic stromal lymphopoietin.