Loss of classical transient receptor potential 6 channel reduces allergic airway response.

Abstract

BACKGROUND:

Non-selective cation influx through canonical transient receptor potential channels (TRPCs) is thought to be an important event leading to airway inflammation. TRPC6 is highly expressed in the lung, but its role in allergic processes is still poorly understood.

OBJECTIVE:

The purpose of this study was to evaluate the role of TRPC6 in airway hyperresponsiveness (AHR) and allergic inflammation of the lung.

METHODS:

Methacholine-induced AHR was assessed by head-out body plethysmography of wild type (WT) and TRPC6(-/-) mice. Experimental airway inflammation was induced by intraperitoneal ovalbumin (OVA) sensitization, followed by OVA aerosol challenges. Allergic inflammation and mucus production were analysed 24 h after the last allergen challenge.

RESULTS:

Methacholine-induced AHR and agonist-induced contractility of tracheal rings were increased in TRPC6(-/-) mice compared with WT mice, most probably due to compensatory up-regulation of TRPC3 in airway smooth muscle cells. Most interestingly, when compared with WT mice, TRPC6(-/-) mice exhibited reduced allergic responses after allergen challenge as evidenced by a decrease in airway eosinophilia and blood IgE levels, as well as decreased levels of T-helper type 2 (Th2) cytokines (IL-5, IL-13) in the bronchoalveolar lavage. However, lung mucus production after allergen challenge was not altered by TRPC6 deficiency.

CONCLUSIONS:

TRPC6 deficiency inhibits specific allergic immune responses, pointing to an important immunological function of this cation channel in Th2 cells, eosinophils, mast cells and B cells.

• Authors: S Sel, B R Rost, A O Yildirim, B Sel, H Kalwa, H Fehrenbach, H Renz, T Gudermann, A Dietrich
• Journal: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology (Clin Exp Allergy) Vol. 38 Issue 9 Pg. 1548-58 (Sep 2008) ISSN: 1365-2222 [Electronic] England
• PMID: 18631347 (Publication Type: Journal Article)

Chemical References

• Interleukin-13
• Interleukin-5
• TRPC Cation Channels
• TRPC3 cation channel
• TRPC6 Cation Channel
• Trpc6 protein, mouse
• Immunoglobulin E
• Ovalbumin

Topics

• Animals
• Bronchial Hyperreactivity (immunology, metabolism, physiopathology)
• Cells, Cultured
• Epithelial Cells (metabolism)
• Guinea Pigs
• Hypersensitivity (immunology, metabolism, physiopathology)
• Immunoglobulin E (blood)
• In Vitro Techniques
• Interleukin-13 (metabolism)
• Interleukin-5 (metabolism)
• Leukocytes (pathology)
• Lung (immunology, metabolism)
• Mice
• Mice, Knockout
• Mucus (metabolism)
• Muscle Contraction
• Muscle, Smooth (metabolism, physiopathology)
• Ovalbumin (immunology)
• Pulmonary Eosinophilia (immunology, pathology)
• TRPC Cation Channels (biosynthesis, genetics, physiology)
• TRPC6 Cation Channel
• Trachea (metabolism, physiopathology)