Gene Set: MCDOWELL_ACUTE_LUNG_INJURY_DN

Standard name MCDOWELL_ACUTE_LUNG_INJURY_DN
Systematic name M1650
Brief description Genes down-regulated in the mouse model of acute lung injury induced by inhaling nickel sulfate [PubChem=24586].
Full description or abstract The role of nitric oxide (NO) in acute lung injury remains controversial. Although inhaled NO increases oxygenation in clinical trials, inhibiting NO-synthase (NOS) can be protective. To examine the latter, nickel-exposed mice were treated with saline or NOS inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME). Initial microarray analysis of nickel-induced gene expression of saline-treated mice revealed increased inflammatory mediator, matrix injury-repair, and hypoxia-induced factor-mediated sequences and decreased lung-specific (e.g., surfactant-associated protein B and C) sequences. Compared with saline control, L-NAME-treated mice had enhanced survival with attenuated serum nitrate/nitrite, endothelial NOS activity, and lavage neutrophils and protein. Although initial cytokine (i.e., interferon-gamma, interleukins-1beta and -6, macrophage inflammatory protein-2, monocyte chemotactic protein-1, and tumor necrosis factor-alpha) gene expression was similar between groups, subsequent larger cytokine increases only occurred in saline-treated mice. Similarly, surfactant protein gene expression decreased initially in both groups yet was restored subsequently with L-NAME treatment. Interestingly, the role of inducible NOS (iNOS) in these responses seems minimal. iNOS gene expression was unaltered, iNOS activity and nitrotyrosine residues were undetectable, and an iNOS antagonist, aminoguanidine, failed to increase survival. Rather, systemic L-NAME treatment appears to attenuate pulmonary endothelial NOS activity, subsequent cytokine expression, inflammation, and protein permeability, and thereby restores surfactant gene expression and increases survival.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 12540486   Authors: McDowell SA,Gammon K,Zingarelli B,Bachurski CJ,Aronow BJ,Prows DR,Leikauf GD
Exact source Table 2
Related gene sets (show 1 additional gene sets from the source publication)

(show 14 gene sets from the same authors)
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Organism Mus musculus
Contributed by John Newman (University of Washington)
Source platform SEQ_ACCESSION
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Version history 3.1: First introduced

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