A Novel Role for Brain Natriuretic Peptide: Inhibition of IL-1 Secretion via Downregulation of NF-kB/Erk 1/2 and NALP3/ASC/Caspase-1 Activation in Human THP-1 Monocyte

Figure 7

Mechanism of action of BNP inhibitory effect on LPS/ATP-induced IL-1β secretion in human THP-1 monocyte. BNP/NPR1/cGMP axis strongly inhibits IL-1β secretion by acting both at transcriptional and at posttranslational level. Firstly, by inhibiting the activation of NF-kB and ERK 1/2 signaling pathway, BNP downregulates the production of the inactive cytoplasmic precursor pro-IL-1β. Subsequently, again by inhibiting NF-kB and ERK 1/2 activation, BNP strongly downregulates all the elements of NALP3 inflammasome/ASC/Caspase-1 cascade and Caspase -1 activation, essential steps for the formation of the active secreted IL-1β protein.