Subcutaneous prostaglandin E(2) restrains airway mast cell activity in vivo and reduces lung eosinophilia and Th(2) cytokine overproduction in house dust mite-sensitive mice.

Abstract

BACKGROUND:

Prostaglandin (PG) E(2) is thought to exert protective effects in the lungs. Accordingly, aerosolized PGE(2) prevents the experimentally induced airway response to allergen challenge in asthmatics. In vitro evidence indicating that functional PGE(2) receptors (EP) are expressed on human mast cells and that PGE(2) can alter cytokine production suggests that these phenomena may be involved in its beneficial effect in asthma. However, in vivo evidence is scarce.

METHODS:

We assessed the effects of exogenous PGE(2) and of the EP1/EP3 agonist sulprostone on the murine airway response to house dust mite (HDM) allergens, a model that accurately reproduces the spontaneous exposure of allergic asthma patients to aeroallergens. We also analyzed the in vivo impact of PGE(2) on production in the murine airway of mast cell protease (mMCP)-1, a specific marker of lung mast cell activity, and on local production of cytokines.

RESULTS:

Exogenous PGE(2), but not sulprostone, reduced eosinophilic infiltration in HDM-sensitized mice by half and led to a strong reduction in airway Th(2) cytokine expression. These anti- inflammatory effects were accompanied in vivo by a substantial reduction in HDM-induced upregulation of airway mMCP-1. Neither PGE(2) nor sulprostone had any effect on airway hyperresponsiveness to methacholine.

CONCLUSIONS:

Our results indicate that the anti-inflammatory effect of PGE(2) can be reproduced in vivo in HDM-sensitized mice and suggest that this protective effect is dependent in vivo on inhibition of the allergen-triggered proinflammatory activity of bronchial mast cells. Finally, the effect of PGE(2) is linked to reduced upregulation of airway Th(2) cytokines.

• Authors: Aida Herrerias, Rosa Torres, Mariona Serra, Alberto Marco, Jordi Roca-Ferrer, César Picado, Fernando de Mora
• Journal: International archives of allergy and immunology (Int Arch Allergy Immunol) Vol. 149 Issue 4 Pg. 323-32 ( 2009) ISSN: 1423-0097 [Electronic] Switzerland
• PMID: 19295236 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright (C) 2009 S. Karger AG, Basel.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Ccl2 protein, mouse
• Chemokine CCL2
• Cytokines
• PTGER1 protein, human
• PTGER3 protein, human
• Ptger1 protein, mouse
• Ptger3 protein, mouse
• Receptors, Prostaglandin E
• Receptors, Prostaglandin E, EP1 Subtype
• Receptors, Prostaglandin E, EP3 Subtype
• Methacholine Chloride
• sulprostone
• Dinoprostone

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (administration & dosage, therapeutic use)
• Asthma (drug therapy, etiology)
• Chemokine CCL2 (antagonists & inhibitors, biosynthesis)
• Cytokines (biosynthesis)
• Dinoprostone (administration & dosage, analogs & derivatives, therapeutic use)
• Disease Models, Animal
• Eosinophils (drug effects, immunology, metabolism)
• Female
• Infusions, Subcutaneous
• Lung (drug effects, immunology, pathology)
• Mast Cells (drug effects, immunology, metabolism)
• Methacholine Chloride (pharmacology)
• Mice
• Mice, Inbred BALB C
• Pulmonary Eosinophilia (drug therapy, immunology)
• Pyroglyphidae (immunology)
• Receptors, Prostaglandin E (agonists, biosynthesis)
• Receptors, Prostaglandin E, EP1 Subtype
• Receptors, Prostaglandin E, EP3 Subtype
• Th2 Cells (immunology)