The mechanism of nicotinamide on reducing acute lung injury by inhibiting MAPK and NF-κB signal pathway

Abstract

Background Acute lung injury is an important factor that leads to the death of patients with pneumonia. Previous studies have shown that nicotinamide (NAM) plays a role in reducing cell damage, so this study explored the mechanism by which NAM functions in acute lung injury. Methods We explored the mechanism by which NAM affects acute lung injury in vivo and in vitro by qRT-PCR, western blotting and ELISA. Results The results showed that NAM could significantly reduce lung injury and proinflammatory mediator accumulation. Further mechanistic studies showed that NAM could significantly inhibit the MAPK and AKT/NF-κB signaling pathways. Conclusion These results suggested that NAM may reduce the release of proinflammatory mediators by inhibiting the MAPK and AKT/NF-κB signaling pathways and ultimately alleviate lung injury.

Nicotinamide breaks effector CD8 T cell responses by targeting mTOR signaling

“…However, NAM can be reconverted to NAD + , which is a SIRT1 activator ( Hwang and Song, 2017 ). Furthermore, recent work have shed light on other molecular pathways possibly targeted by NAM ( Daniel et al., 2007 ; Meng et al., 2018 ; Mouchiroud et al., 2013 ; Van Gool et al., 2009 ; Zhang et al., 2021 ). However, the mechanism by which NAM reduces cytokine production in T cells is unknown.…”

“…In mouse hepatocytes, NAM-dependent increase of NAD + induces the activation of the antioxidant gene FOXO, improving metabolic health, and extending life span ( Mouchiroud et al., 2013 ). In addition, NAM plays an inhibitory role on ROCK/CK1 kinases in human pluripotent stem cells ( Meng et al., 2018 ), on ERK phosphorylation in B cells ( Daniel et al., 2007 ), on SIRT6 activity in macrophages and dendritic cells ( Van Gool et al., 2009 ), and on MAPK and NF-κB activity in macrophages ( Zhang et al., 2021 ). In this study, we show that the molecular mechanism by which NAM reduces IFNγ in CD8 + effector T cells is dependent on the mTORC1 pathway through AMPK activation ( Figures 4 A–4D).…”

“…S. aureus enterotoxin A is a superantigen that activates specific TCR Vβ T cells ( Herman et al., 1991 ) and induces acute lung injury ( Kumar et al., 2010 ; Li et al., 2020 ; Menoret et al., 2018 ; Svedova et al., 2017 ), exerting a major effect on CD8 + T cells infiltration and IFNγ production ( Muralimohan et al., 2008 ). Other studies have addressed the effect of NAM in innate immune and inflammatory responses against acute lung injury ( Su et al., 2007 ; Zhang et al., 2021 ). However, the role of NAM on the adaptive arm is completely unknown.…”

Signaling pathways and potential therapeutic targets in acute respiratory distress syndrome (ARDS)

“…Inactivation of MAPK signaling is also demonstrated to contribute to the anti-inflammatory effects in ARDS treatment. Nicotinamide [ 101 ], Irigenin [ 259 ] and β-Caryophyllene [ 260 ] have been recently found to inhibit MAPK signaling and reduce expression of inflammatory factors in ALI model. Particularly, Dilmapimod, a specific p38MAPK inhibitor, has been reported to have a satisfactory safety profile in trauma patients at risk of developing ARDS and to reduce the concentration of pro-inflammatory cytokines [ 261 ].…”

Anti-cancer and immunomodulatory evaluation of new nicotinamide derivatives as potential VEGFR-2 inhibitors and apoptosis inducers: in vitro and in silico studies

“…In many publications, nicotinamide moiety was reported as potent inhibitor of proinflammatory cytokines (TNF α and IL-6) 20 , 24 , 25 . These reports revealed that nicotinamide has a potent immunomodulatory activity and may have promising effect for the treatment of inflammatory disease as cancer 20 .…”