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

Abstract

Interleukin-1β (IL-1β) is a pleiotropic cytokine and a crucial mediator of inflammatory and immune responses. IL-1β processing and release are tightly controlled by complex pathways such as NF-kB/ERK1/2, to produce pro-IL-1β, and NALP3/ASC/Caspase-1 inflammasome, to produce the active secreted protein. Dysregulation of both IL-1β and its related pathways is involved in inflammatory/autoimmune disorders and in a wide range of other diseases. Identifying molecules modulating their expression is a crucial need to develop new therapeutic agents. IL-1β is a strong regulator of Brain Natriuretic Peptide (BNP), a hormone involved in cardiovascular homeostasis by guanylyl cyclase Natriuretic Peptide Receptor (NPR-1). An emerging role of BNP in inflammation and immunity, although proposed, remains largely unexplored. Here, we newly demonstrated that, in human THP-1 monocytes, LPS/ATP-induced IL-1β secretion is strongly inhibited by BNP/NPR-1/cGMP axis at all the molecular mechanisms that tightly control its production and release, NF-kB, ERK 1/2, and all the elements of NALP3/ASC/Caspase-1 inflammasome cascade, and that NALP3 inflammasome inhibition is directly related to BNP deregulatory effect on NF-kB/ERK 1/2 activation. Our findings reveal a novel potent anti-inflammatory and immunomodulatory role for BNP and open new alleys of investigation for a possible employment of this endogenous agent in the treatment of inflammatory/immune-related and IL-1β/NF-kB/ERK1/2/NALP3/ASC/Caspase-1-associated diseases.

Melatonin alleviates intervertebral disc degeneration by disrupting the IL-1β/NF-κB-NLRP3 inflammasome positive feedback loop

“…51 There are some studies concerning NLRP3 inflammasome regulation, and various pathways, including the Smad, NFAT, NF-κB, and MAP kinase pathways, regulate NLRP3 expression. 57,58 Yu et al showed that hepatitis B e antigen suppresses LPS-induced NLRP3 inflammasome activation and IL-1β production by repressing NLRP3 and pro-IL-1β expression through inhibition of NF-κB phosphorylation and by repressing caspase-1 activation and IL-1β maturation through inhibition of ROS production. 59 Budai et al also reported that LPS induces NLRP3 inflammasome regulation through the NF-κB, p38, JNK, and ERK signaling pathways.…”

High brain natriuretic peptide is associated with sarcopenia in patients with type 2 diabetes: a cross-sectional study of KAMOGAWA-DM cohort study

“…Moreover, BNP levels themselves are associated with the inflammation and it was reported that the secretion of BNP is induced by increased TNF-α [39,40]. BNP is known as an antiinflammatory hormone [41][42][43]. Therefore, the associa- tion of high BNP and sarcopenia apparently seems contradictory.…”

The synergistic effect of propofol and ulinastatin suppressed the viability of the human lung adenocarcinoma epithelial A549 cell line

“…PPF → ulinastatin synergistic antitumor effects may be importantly related to the immune microenvironment. As ERK1/2 phosphorylation is an important step for cytokine secretion such as TNF-α ( 30 ) and IL-1β ( 31 ), PPF → ulinastatin may synergistically reduce cytokine secretion of TNF-α and IL-1β by inhibiting ERK1/2 phosphorylation in A549 cells.…”