Dietary abscisic acid ameliorates influenza-virus-associated disease and pulmonary immunopathology through a PPARγ-dependent mechanism.

Abstract

The anti-inflammatory phytohormone abscisic acid (ABA) modulates immune and inflammatory responses in mouse models of colitis and obesity. ABA has been identified as a ligand of lanthionine synthetase C-like 2, a novel therapeutic target upstream of the peroxisome proliferator-activated receptor γ (PPARγ) pathway. The goal of this study was to investigate the immune modulatory mechanisms underlying the anti-inflammatory efficacy of ABA against influenza-associated pulmonary inflammation. Wild-type (WT) and conditional knockout mice with defective PPARγ expression in lung epithelial and hematopoietic cells (cKO) treated orally with or without ABA (100 mg/kg diet) were challenged with influenza A/Udorn (H3N2) to assess ABA's impact in disease, lung lesions and gene expression. Dietary ABA ameliorated disease activity and lung inflammatory pathology, accelerated recovery and increased survival in WT mice. ABA suppressed leukocyte infiltration and monocyte chemotactic protein 1 mRNA expression in WT mice through PPARγ since this effect was abrogated in cKO mice. ABA ameliorated disease when administered therapeutically on the same day of the infection to WT but not mice lacking PPARγ in myeloid cells. We also show that ABA's greater impact is between days 7 and 10 postchallenge when it regulates the expression of genes involved in resolution, like 5-lipoxygenase and other members of the 5-lipoxygenase pathway. Furthermore, ABA significantly increased the expression of the immunoregulatory cytokine interleukin-10 in WT mice. Our results show that ABA, given preventively or therapeutically, ameliorates influenza-virus-induced pathology by activating PPARγ in pulmonary immune cells, suppressing initial proinflammatory responses and promoting resolution.

• Authors: Raquel Hontecillas, Paul C Roberts, Adria Carbo, Cristina Vives, William T Horne, Sandra Genis, Binu Velayudhan, Josep Bassaganya-Riera
• Journal: The Journal of nutritional biochemistry (J Nutr Biochem) Vol. 24 Issue 6 Pg. 1019-27 (Jun 2013) ISSN: 1873-4847 [Electronic] United States
• PMID: 22995385 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Chemokine CCL2
• PPAR gamma
• Interleukin-10
• Abscisic Acid

Topics

• Abscisic Acid (administration & dosage, pharmacology)
• Animals
• Anti-Inflammatory Agents (administration & dosage, pharmacology)
• Chemokine CCL2 (metabolism)
• Diet
• Epithelial Cells (immunology, metabolism)
• Influenza A Virus, H3N2 Subtype (drug effects, physiology)
• Interleukin-10 (metabolism)
• Leukocytes (immunology)
• Lung (immunology, metabolism, pathology)
• Mice
• Mice, Knockout
• Myeloid Cells (immunology, metabolism)
• Orthomyxoviridae Infections (drug therapy, immunology, pathology)
• PPAR gamma (genetics, metabolism)
• Pneumonia (drug therapy, immunology, pathology)
• Respiratory Mucosa (immunology, metabolism, pathology)
• Virus Replication