A synthetic cationic antimicrobial peptide inhibits inflammatory response and the NLRP3 inflammasome by neutralizing LPS and ATP

Abstract

Antimicrobial peptides (AMPs) are one of the most important defense mechanisms against bacterial infections in insects, plants, non-mammalian vertebrates, and mammals. In the present study, a class of synthetic AMPs was evaluated for anti-inflammatory activity. One cationic AMP, GW-A2, demonstrated the ability to inhibit the expression levels of nitric oxide (NO), inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in lipopolysaccharide (LPS)-activated macrophages. GW-A2 reduced LPS-induced increases in the phosphorylation of mitogen-activated protein kinase and protein kinase C-α/δ and the activation of NF-κB. GW-A2 also inhibited NLRP3 inflammasome activation induced by LPS and ATP. Furthermore, in the mice injected with LPS, GW-A2 reduced (1) the concentration of IL-1β, IL-6 and TNF-α in the serum; (2) the concentration of TNF-α in the peritoneal lavage; (3) the expression levels of iNOS, COX-2 and NLRP3 in the liver and lung; (4) the infiltration of polymorphonuclear neutrophils in the liver and lung. The underlying mechanisms for the anti-inflammatory activity of GW-A2 were found to be partially due to LPS and ATP neutralization. These results provide insights into how GW-A2 inhibits inflammation and the NLRP3 inflammasome and provide a foundation for the design of rational therapeutics for inflammation-related diseases.

Synthetic 4-Hydroxy Auxarconjugatin B, a Novel Autophagy Inducer, Attenuates Gouty Inflammation by Inhibiting the NLRP3 Inflammasome

“…However, little is known about the effects of 4-HAB on the NLRP3 inflammasome and the underlying molecular mechanism of these effects. As part of our efforts is to identify novel NLRP3 inflammasome inhibitors [11][12][13][14][15] and based on the known anti-inflammatory effects of 4-HAB, we hypothesized that 4-HAB can inhibit the NLRP3 inflammasome.…”

Poly-arginine R18 and R18D (D-enantiomer) peptides reduce infarct volume and improves behavioural outcomes following perinatal hypoxic-ischaemic encephalopathy in the P7 rat

“…Similarly, due to the damaging effects of MMPs on the neurovascular unit and blood brain barrier, any down-regulation of their proteolytic activity is likely to be beneficial following brain HI. In addition, there is also evidence that CARPs can activate pro-survival signaling pathways [ 17 , 41 ] and modulate immune responses [ 42 – 44 ], as well as act as anti-oxidant molecules in their own right due to their guanidino group containing arginine residues [ 32 , 45 – 49 ].…”

Eucalyptus essential oils inhibit the lipopolysaccharide-induced inflammatory response in RAW264.7 macrophages through reducing MAPK and NF-κB pathways

“…RAW-Blue macrophages were purchased from Invivo-Gen (San Diego, CA). All cells were propagated in RPMI 1640 supplemented with 10% (v/v) heatinactivated FBS and 2 mM L-glutamine at 37°C in a 5% CO 2 incubator [16,17].…”