beta6 Integrin subunit deficiency alleviates lung injury in a mouse model of bronchopulmonary dysplasia.
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.
Hogmalm
Anna
A
University of Gothenburg, Department of Pediatrics, the Queen Silvia Children's Hospital, SWE-416 85 Gothenburg, Sweden.
Sheppard
Dean
D
Lappalainen
Urpo
U
Bry
Kristina
K
D000818:Animals; D001997:Bronchopulmonary Dysplasia / Q000378:metabolism* / Q000473:pathology; D018925:Chemokines / Q000378:metabolism; D004195:Disease Models, Animal; D004318:Doxycycline / Q000494:pharmacology; D006801:Humans; D007231:Infant, Newborn / Q000276:immunology; D039641:Integrin beta Chains / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology; D008171:Lung Diseases / Q000378:metabolism; D055370:Lung Injury / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D051381:Rats
D018925:Chemokines; D039641:Integrin beta Chains; D053583:Interleukin-1beta; C072170:integrin beta6; D004318:Doxycycline