Mechanisms of inflammatory lung injury in the neonate: lessons from a transgenic mouse model of bronchopulmonary dysplasia.
The role of inflammation in the pathogenesis of bronchopulmonary dysplasia (BPD) is not well understood. By using a transgenic mouse expressing the inflammatory cytokine interleukin (IL)-1beta in the lung, we have shown that perinatal expression of IL-1beta causes a BPD-like illness in infant mice. We have used this model to identify mechanisms by which inflammation causes neonatal lung injury. Increased matrix metalloproteinase (MMP)-9 activity is associated with BPD. MMP-9 deficiency worsens alveolar hypoplasia in IL-1beta-expressing newborn mice, suggesting that MMP-9 has a protective role in neonatal inflammatory lung injury. The beta6 integrin subunit, an activator of transforming growth factor-beta, is involved in adult lung disease. Absence of the beta6 integrin subunit improves alveolar development in IL-1beta-expressing mice, suggesting that the beta6 integrin subunit is a pathogenetic factor in inflammatory lung disease in the newborn. The authors of clinical studies who have examined maternal inflammation as a risk factor for BPD have found variable results. We have shown that maternal IL-1beta production preceding fetal IL-1beta production prevents lung inflammation, alveolar hypoplasia, and airway remodeling in newborn IL-1beta-expressing mice. Thus, maternal inflammation may protect the newborn lung against subsequent inflammatory injury. In contrast, when maternal and fetal production of IL-1beta are induced simultaneously, the development of IL-1beta-induced lung disease in the newborn is not prevented.
Bry
Kristina
K
Department of Pediatrics, University of Gothenburg, Gothenburg, Sweden. kristina.bry@pediat.gu.se
Hogmalm
Anna
A
Bäckström
Erica
E
D056151:Airway Remodeling; D000818:Animals; D000831:Animals, Newborn; D001997:Bronchopulmonary Dysplasia / Q000473:pathology / Q000503:physiopathology*; D002821:Chorioamnionitis / Q000503:physiopathology; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007249:Inflammation; D039641:Integrin beta Chains / Q000502:physiology; D053583:Interleukin-1beta / Q000502:physiology; D008168:Lung / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D011247:Pregnancy; D047928:Premature Birth / Q000209:etiology; D053773:Transforming Growth Factor beta1 / Q000502:physiology
D039641:Integrin beta Chains; D053583:Interleukin-1beta; D053773:Transforming Growth Factor beta1; C072170:integrin beta6; D020780:Matrix Metalloproteinase 9