Specific Peptide Surface Coating: A Hint to Tune the Inflammatory Response of Nano CrystalsPengfei W1,2,4, Mengru L3, Yi Hu1 and Longpingwen1,2*
1The CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Signaling Network, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China
- *Corresponding Author:
The CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Signaling Network
School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China
E-mail: [email protected]
Received date: January 15, 2017; Accepted date: March 08, 2017; Published date: April 06, 2017
Citation: Pengfei W, Mengru L, Yi Hu, Longpingwen (2017) Specific Peptide Surface Coating: A Hint to Tune the Inflammatory Response of Nano Crystals. J Mucosal Immunol Res 1:101.
Copyright: © 2017 Pengfei W, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
We provided a comprehensive line of evidence indicating Lanthanide-based nanoparticles elicited NLRP3 dependent inflammasome activation in vitro and inflammatory response in vivo. A short synthetic peptide identified by our group, RE-1(ACTARSPWICG), could form a stable coating layer on the surface of Lanthanide-based nanoparticles (LNs) through specifically binding and effectively block their autophagy-inducing activity and liver toxicity. Recently, RE-1 coating were also demonstrated to significantly abrogate LN-elicited inflammasome activation without influencing cell uptake of nanocrystals in macrophage cells, and inflammatory response in peritoneal cavity. Furthermore, the mechanism of the inflammasome-inhibiting effect of RE-1 coating was investigated. RE-1 coating did not effectively reduce LN-elicited potassium efflux, while the potassium channel inhibitor glibenclamide did, indicating that potassium efflux was necessary but insufficient for LN-induced inflammasome activation. RE-1 did reduce lysosomal damage induced by LNs, However, the inhibitor of cathepsin B could not alter LN-elicited caspase-1 activation and IL-1β release, indicating that lysosomal damage was not critically important for LN-induced inflammasome activation. In contrast, RE-1 could dramatically inhibit LN-induced up-regulation of intracellular reactive oxygen species (ROS), greatly important for inflammasome activation. And, the reduction on NADPH oxidase-generated ROS was more critical for RE-1's inflammasome-inhibiting effect than the reduction on mitochondria-generated ROS. ROS generation further triggered Transient Receptor Potential M2 (TRPM2) regulated Ca2+ influx to induce inflammasome activation, which could be completely canceled by RE-1 coating. In conclusion, RE-1 primarily inhibited NADPH oxidase regulated ROS generation and subsequently curbed TRPM2-mediated Ca2+ influx to abrogate LN-induced inflammasome activation. Our study gives a new direction to modulate the inflammatory response of nanocrystals to realize immune escape via surface peptide coating, great value for in vivo applications of engineered nanomaterials.