| First Author | Hou Y | Year | 2015 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 309 |
| Issue | 6 | Pages | L593-604 |
| PubMed ID | 26163511 | Mgi Jnum | J:232526 |
| Mgi Id | MGI:5779481 | Doi | 10.1152/ajplung.00029.2015 |
| Citation | Hou Y, et al. (2015) Activation of the nuclear factor-kappaB pathway during postnatal lung inflammation preserves alveolarization by suppressing macrophage inflammatory protein-2. Am J Physiol Lung Cell Mol Physiol 309(6):L593-604 |
| abstractText | A significant portion of lung development is completed postnatally during alveolarization, rendering the immature lung vulnerable to inflammatory stimuli that can disrupt lung structure and function. Although the NF-kappaB pathway has well-recognized pro-inflammatory functions, novel anti-inflammatory and developmental roles for NF-kappaB have recently been described. Thus, to determine how NF-kappaB modulates alveolarization during inflammation, we exposed postnatal day 6 mice to vehicle (PBS), systemic lipopolysaccharide (LPS), or the combination of LPS and the global NF-kappaB pathway inhibitor BAY 11-7082 (LPS + BAY). LPS impaired alveolarization, decreased lung cell proliferation, and reduced epithelial growth factor expression. BAY exaggerated these detrimental effects of LPS, further suppressing proliferation and disrupting pulmonary angiogenesis, an essential component of alveolarization. The more severe pathology induced by LPS + BAY was associated with marked increases in lung and plasma levels of macrophage inflammatory protein-2 (MIP-2). Experiments using primary neonatal pulmonary endothelial cells (PEC) demonstrated that MIP-2 directly impaired neonatal PEC migration in vitro; and neutralization of MIP-2 in vivo preserved lung cell proliferation and pulmonary angiogenesis and prevented the more severe alveolar disruption induced by the combined treatment of LPS + BAY. Taken together, these studies demonstrate a key anti-inflammatory function of the NF-kappaB pathway in the early alveolar lung that functions to mitigate the detrimental effects of inflammation on pulmonary angiogenesis and alveolarization. Furthermore, these data suggest that neutralization of MIP-2 may represent a novel therapeutic target that could be beneficial in preserving lung growth in premature infants exposed to inflammatory stress. |
