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Effects of age on the synergistic interactions between lipopolysaccharide and mechanical ventilation in mice.
Title | Effects of age on the synergistic interactions between lipopolysaccharide and mechanical ventilation in mice. |
Publication Type | Journal Article |
Year of Publication | 2010 |
Authors | Smith, LS, Gharib, SA, Frevert, CW, Martin, TR |
Journal | Am J Respir Cell Mol Biol |
Volume | 43 |
Issue | 4 |
Pagination | 475-86 |
Date Published | 2010 Oct |
ISSN | 1535-4989 |
Keywords | Aging, Animals, Cluster Analysis, Cytokines, Female, Gene Expression Profiling, Gene Expression Regulation, Gene Regulatory Networks, Lipopolysaccharides, Lung, Male, Mice, Mice, Inbred C57BL, Multigene Family, Neutrophils, Permeability, Pneumonia, Principal Component Analysis, Respiration, Artificial, Transcription, Genetic |
Abstract | Children have a lower incidence and mortality from acute lung injury (ALI) than adults, and infections are the most common event associated with ALI. To study the effects of age on susceptibility to ALI, we investigated the responses to microbial products combined with mechanical ventilation (MV) in juvenile (21-d-old) and adult (16-wk-old) mice. Juvenile and adult C57BL/6 mice were treated with inhaled Escherichia coli 0111:B4 lipopolysaccharide (LPS) and MV using tidal volume = 15 ml/kg. Comparison groups included mice treated with LPS or MV alone and untreated age-matched control mice. In adult animals treated for 3 hours, LPS plus MV caused synergistic increases in neutrophils (P < 0.01) and IgM in bronchoalveolar lavage fluid (P = 0.03) and IL-1β in whole lung homogenates (P < 0.01) as compared with either modality alone. Although juvenile and adult mice had similar responses to LPS or MV alone, the synergistic interactions between LPS and MV did not occur in juvenile mice. Computational analysis of gene expression array data suggest that the acquisition of synergy with increasing age results, in part, from the loss of antiapoptotic responses and the acquisition of proinflammatory responses to the combination of LPS and MV. These data suggest that the synergistic inflammatory and injury responses to inhaled LPS combined with MV are acquired with age as a result of coordinated changes in gene expression of inflammatory, apoptotic, and TGF-β pathways. |
DOI | 10.1165/rcmb.2009-0039OC |
Alternate Journal | Am. J. Respir. Cell Mol. Biol. |
PubMed ID | 19901347 |
PubMed Central ID | PMC2951878 |
Grant List | HL072370 / HL / NHLBI NIH HHS / United States HL073996-01 / HL / NHLBI NIH HHS / United States HL074223 / HL / NHLBI NIH HHS / United States HL081764 / HL / NHLBI NIH HHS / United States K08 HL094750 / HL / NHLBI NIH HHS / United States K08 HL094750-03 / HL / NHLBI NIH HHS / United States |