beta6 Integrin subunit deficiency alleviates lung injury in a mouse model of bronchopulmonary dysplasia.

Abstract

Pulmonary inflammation is associated with the development of bronchopulmonary dysplasia in premature infants. We have previously shown that perinatal pulmonary expression of human IL-1beta is sufficient to cause a lung disease similar to bronchopulmonary dysplasia, characterized by inflammation, impaired alveolarization, poor postnatal growth, and increased mortality in infant mice. The alphavbeta6 integrin plays a critical role in regulating inflammation in the adult lung. To study the role of the beta6 integrin subunit in neonatal inflammatory lung disease, we compared the pulmonary development in IL-1beta-expressing infant mice with wild-type or null beta6 integrin loci. Absence of the beta6 integrin subunit decreased the mortality and improved the postnatal growth of IL-1beta-expressing pups. The disrupted alveolar development of IL-1beta-expressing mice was improved by beta6 integrin deficiency. IL-1beta-expressing beta6(-/-) pups had shorter alveolar chord length and thinner alveolar walls than IL-1beta-expressing beta6(+/+) pups. In addition, the absence of the beta6 integrin subunit reduced IL-1beta-induced neutrophil and macrophage infiltration into the alveolar spaces. beta6 integrin subunit deficiency suppressed inflammation and goblet cell hyperplasia in the airways and alleviated airway remodeling in IL-1beta-expressing mice. The expression of the chemoattractant proteins, keratinocyte-derived chemokine, macrophage-inflammatory protein-2, calgranulin A, and calgranulin B, of osteopontin, and of the chitinase-like lectins, Ym1 and Ym2, was lower in IL-1beta-expressing beta6(-/-) than in IL-1beta-expressing beta6(+/+) mice. We conclude that absence of the beta6 integrin subunit protects the infant murine lung against IL-1beta-induced inflammation and injury.

• Authors: Anna Hogmalm, Dean Sheppard, Urpo Lappalainen, Kristina Bry
• Journal: American journal of respiratory cell and molecular biology (Am J Respir Cell Mol Biol) Vol. 43 Issue 1 Pg. 88-98 (Jul 2010) ISSN: 1535-4989 [Electronic] United States
• PMID: 19717813 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Chemokines
• Integrin beta Chains
• Interleukin-1beta
• integrin beta6
• Doxycycline

Topics

• Animals
• Bronchopulmonary Dysplasia (metabolism, pathology)
• Chemokines (metabolism)
• Disease Models, Animal
• Doxycycline (pharmacology)
• Humans
• Infant, Newborn (immunology)
• Integrin beta Chains (metabolism)
• Interleukin-1beta (metabolism)
• Keratinocytes (cytology)
• Lung Diseases (metabolism)
• Lung Injury (metabolism)
• Macrophages (metabolism)
• Mice
• Mice, Transgenic
• Rats