<p>Dual Role For A MEK Inhibitor As A Modulator Of Inflammation And Host Defense Mechanisms With Potential Therapeutic Application In COPD</p>

• DOI: 10.2147/copd.s211619
• Publication Date: 2019-11-25T18:14:27Z
• Authors: Nisha Kurian; Taylor S Cohen; Lisa Öberg; Erica De Zan; Gabriel Skogberg; Stefan Vollmer; Engin Baturcam; Petter Svanberg; Britta Bonn; Paul D Smith; Outi Vaarala; Danen M Cunoosamy
• Keywords: Adult; Male; 0301 basic medicine; MAP Kinase Kinase 2; MAP Kinase Kinase 1; International Journal of Chronic Obstructive Pulmonary Disease; transcriptomics; Diseases of the respiratory system; Pulmonary Disease, Chronic Obstructive; Young Adult; 03 medical and health sciences; exacerbation; p38 mapk; Humans; Cells, Cultured; Original Research; Aged; Inflammation; RC705-779; steroid; Diphenylamine; sputum; Middle Aged; infection; 3. Good health; Benzamides; Female; alveolar macrophage; Signal Transduction

Background: Unlike p38 mitogen-activated protein Kinases (MAPK) that has been extensively studied in the context of lung-associated pathologies COPD, role dual-specificity kinase (MEK1/2) or its downstream signaling molecule extracellular signal-regulated kinases 1/2 (ERK1/2) COPD is poorly understood. Objectives: The aim this study was to address whether MEK1/2 pathway activation linked and targeting can improve lung inflammation through decreased immune-mediated inflammatory responses without compromising bacterial clearance. Methods: Association investigated by immunohistochemistry using tissue biopsies from healthy individuals analysis sputum gene expression data patients. anti-inflammatory effect inhibition assessed on cytokine release lipopolysaccharide-stimulated alveolar macrophages. clearance Staphylococcus aureus killing assays with RAW 264.7 macrophage cell line human neutrophils. Results: We report here demonstrated increased pERK1/2 staining bronchial epithelium presence MEK signature samples Inhibition resulted a superior macrophages comparison inhibitor. Furthermore, led an increase neutrophils cells not observed Conclusion: Our demonstrate highlight dual function improving host defense whilst also controlling inflammation. Keywords: exacerbation, infection, macrophage, MAPK, steroid, transcriptomics,