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• W2922182117 abstract "Phosphodiesterase 4 (PDE4) inhibitors are used to treat autoimmune and inflammatory diseases, such as psoriasis and chronic obstructive pulmonary disease (COPD). CHF6001 is a novel, potent and selective inhaled PDE4 inhibitor in development for the treatment of COPD. When tested in vitro on human dendritic cells (DCs), CHF6001 decreased the release of pro-inflammatory cytokines (TNF-α and IL-6), chemokines (CXCL8, CCL3, CXCL10 and CCL19) and of Th1- and Th17-polarizing cytokines (IL-12, IL-23 and IL-1β). In contrast to β-methasone, a reference steroid anti-inflammatory drug, CHF6001 increased the secretion of CCL22, a Th2 recruiting chemokine, and the expression of the lymph node homing receptor CCR7. Accordingly, the migration of DCs to CCR7 ligands was increased, while migration to pro-inflammatory chemokines was decreased. Of note, the action of CHF6001 was apparently mediated by a promoter-specific decrease in NF-κB p65 recruitment, independent of perturbation of LPS signalling or NF-κB nuclear translocation. Our results indicate that CHF6001 can modulate DC pro-inflammatory Th1/Th17 polarizing potential by fine tuning the transcriptional activity of the master inflammatory transcription factor NF-κB. Therefore, CHF6001 may prove useful to control Th1/Th17-polarized inflammatory diseases such as COPD." @default.
• W2922182117 created "2019-03-22" @default.
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• W2922182117 date "2019-05-01" @default.
• W2922182117 modified "2023-09-30" @default.
• W2922182117 title "The PDE4 inhibitor CHF6001 modulates pro-inflammatory cytokines, chemokines and Th1- and Th17-polarizing cytokines in human dendritic cells" @default.
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• W2922182117 doi "https://doi.org/10.1016/j.bcp.2019.03.006" @default.
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