Pharmacology research & perspectives
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Pharmacol Res Perspect · Feb 2015
Gene expression changes caused by the p38 MAPK inhibitor dilmapimod in COPD patients: analysis of blood and sputum samples from a randomized, placebo-controlled clinical trial.
The p38 mitogen-activated protein kinase (MAPK) intracellular signaling pathway responds to a variety of extracellular stimuli, including cytokines, Toll-like receptor agonists, and components of cigarette smoke to influence the expression of proinflammatory mediators. Activation of p38 MAPK is increased within the lungs of chronic obstructive pulmonary disease (COPD) patients. In clinical trials, treatment of COPD patients with p38 MAPK inhibitors has been shown to reduce systemic inflammation plasma biomarkers C-reactive protein (CRP) and fibrinogen. ⋯ Whole blood and induced sputum samples were used to measure mRNA levels by gene array and PCR. Pathway and network analysis showed STAT1, MMP-9, CAV1, and IL-1β as genes regulated by dilmapimod that could also influence fibrinogen levels, while only IL-1β was identified as a gene regulated by dilmapimod that could influence CRP levels. This suggests that p38 MAPK inhibits specific inflammatory pathways, leading to to differential effects on CRP and fibrinogen levels in COPD patients.