{'fraction_non_alphanumeric': 0.03396436525612472, 'fraction_numerical': 0.03229398663697105, 'mean_word_length': 5.534545454545454, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
p38 Mitogen-activated protein kinase up-regulates LPS-induced NF-kappaB activation in the development of lung injury and RAW 264.7 macrophages.

Clarification of the key regulatory steps that lead to nuclear factor-kappa B (NF-kappaB) under cellular and pathological conditions is very important. The action of p38 mitogen-activated protein kinase (MAPK) on the upstream of NF-kappaB activation remains controversial. To examine this issue using an in vivo lung injury model, SB203580, a p38 MAPK inhibitor was given intraorally 1h prior to lipopolysaccharide (LPS) treatment (intratracheally). The mice were sacrificed 4 h after LPS treatment. SB203580 substantially suppressed LPS-induced rises in p38 MAPK phosphorylation, neutrophil recruitment, total protein content in bronchoalveolar lavage fluid, and apoptosis of bronchoalveolar cells. Furthermore, SB203580 blocked LPS-induced NF-kappaB activation in lung tissue through down-regulation of serine phosphorylation, degradation of IkappaB-alpha, and consequent translocation of the p65 subunit of NF-kappaB to the nucleus. It is likely that, in cultured RAW 264.7 macrophages, SB203580 also blocked LPS-induced NF-kappaB activation in a dose-dependent manner. SB203580 inhibited LPS-induced serine phosphorylation, degradation of IkappaB-alpha, and tyrosine phosphorylation of p65 NF-kappaB. These data indicate that p38 MAPK acts upstream of LPS-induced NF-kappaB activation by modulating the phosphorylation of IkappaB-alpha and p65 NF-kappaB during acute lung injury. Because LPS-stimulated macrophages may contribute to inflammatory lung injury, the inhibition of the p38 MAPK-mediated intracellular signaling pathway leading to NF-kappaB activation represents a target for the attenuation of lung inflammation and parenchymal damage.