3,4-Methylenedioxy-β-nitrostyrene Inhibits NLRP3 Inflammasome Activation by Blocking Assembly of the Inflammasome

He, Yuan; Varadarajan, Saranyaraajan; Muñoz-Planillo, Raúl; Burberry, Aaron; Nakamura, Yuumi; Núñez, Gabriel

doi:10.1074/jbc.m113.515080

Cited by 235 publications

(211 citation statements)

References 47 publications

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“…NS, not significant. after LPS priming followed by silica stimulation, whereas the opposite behavior was observed for IL-1␤ secretion (47). Leptin also increased IL-18 secretion by human monocytes, while the same effect was not observed for IL-1␤ secretion (48).…”

Section: Discussionmentioning

confidence: 82%

The Tick Salivary Protein Sialostatin L2 Inhibits Caspase-1-Mediated Inflammation during Anaplasma phagocytophilum Infection

et al. 2014

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i Saliva from arthropod vectors facilitates blood feeding by altering host inflammation. Whether arthropod saliva counters inflammasome signaling, a protein scaffold that regulates the activity of caspase-1 and cleavage of interleukin-1␤ (IL-1␤) and IL-18 into mature molecules, remains elusive. In this study, we provide evidence that a tick salivary protein, sialostatin L2, inhibits inflammasome formation during pathogen infection. We show that sialostatin L2 targets caspase-1 activity during host stimulation with the rickettsial agent Anaplasma phagocytophilum. A. phagocytophilum causes macrophage activation and hemophagocytic syndrome features. The effect of sialostatin L2 in macrophages was not due to direct caspase-1 enzymatic inhibition, and it did not rely on nuclear factor B or cathepsin L signaling. Reactive oxygen species from NADPH oxidase and the Loop2 domain of sialostatin L2 were important for the regulatory process. Altogether, our data expand the knowledge of immunoregulatory pathways of tick salivary proteins and unveil an important finding in inflammasome biology.

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Section: Discussionmentioning

confidence: 82%

The Tick Salivary Protein Sialostatin L2 Inhibits Caspase-1-Mediated Inflammation during Anaplasma phagocytophilum Infection

et al. 2014

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“…127 In the screening of a kinase inhibitor library in another recent study, 3,4-methylenedioxy-b-nitrostyrene (MNS) was identified by the prevention of NLRP3-mediated ASC speck formation through targeting NLRP3 or NLRP3-associated complexes. 128 It is also noted that caspase-1, in spite of its essential role in the assembly of NLRP3 inflammasome, is found to play a critical regulatory role in house dust mite-induced allergic lung inflammation through downregulation of IL-33. 129 Recent studies have identified a key role of autophagy in activation of the NLRP3 inflammasome.…”

Section: Negative Regulation Of Nlrp3 Inflammasome Complex Activationmentioning

confidence: 99%

Molecular mechanisms regulating NLRP3 inflammasome activation

et al. 2015

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“…Specific mono-and di-substitutions on the aromatic ring of β-nitrostyrene tended to increase the anti-platelet activity and decrease the cytotoxic activity [17]. 3,4-Methylenedioxy-β-nitrostyrene (MNS) blocks the assembly of NLRP3 inflammasome by the inhibition of NLRP3 ATPase activity [18,19]. The nitrovinyl group is essential for the inhibitory activity of MNS.…”

Section: Mechanism Of Antibacterial Activitymentioning

confidence: 99%

Comparisons of Halogenated β-Nitrostyrenes as Antimicrobial Agents

et al. 2014

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Abstract:The influence of three types of halogen-substituted E-β-methyl-β-nitrostyrenes (such as Compounds B, D, H) to overcome bacterial activity that is currently a significant health threat was studied. The evaluations of their bio-potency was measured and related to their structure and activity relationships for the purposes of serving to inhibit and overcoming resistant microorganisms. In particular, fluorine-containing β-nitrostyrenes were found to be highly active antimicrobial agents. The addition of the β-bromo group enhanced the antibacterial activity significantly. Our work has illustrated that halogen substituents at both the 4-position in the aromatic ring and also at the β-position on the alkene side chain of nitropropenyl arenes enhanced the antimicrobial activity of these compounds.

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3,4-Methylenedioxy-β-nitrostyrene Inhibits NLRP3 Inflammasome Activation by Blocking Assembly of the Inflammasome

Cited by 235 publications

References 47 publications

The Tick Salivary Protein Sialostatin L2 Inhibits Caspase-1-Mediated Inflammation during Anaplasma phagocytophilum Infection

The Tick Salivary Protein Sialostatin L2 Inhibits Caspase-1-Mediated Inflammation during Anaplasma phagocytophilum Infection

Molecular mechanisms regulating NLRP3 inflammasome activation

Comparisons of Halogenated β-Nitrostyrenes as Antimicrobial Agents

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