The Modulatory Activity of Tryptophan Displaying Nanodevices on Macrophage Activation for Preventing Acute Lung Injury

Frontiers in Immunology

Chenchen Wu¹  Shan-Yu Fung²  Huiqiang Ma³  Jiameng Gong³  Liya Sun³  Rui Wang³  Hong Yang³ 

[1] Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China;Key Laboratory of Immune Microenvironment and Disease of the Ministry of Education and Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China;School of Biomedical Engineering and The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University, Tianjin, China;

关键词: immunomodulatory nanoparticles;    acute lung injury;    Toll-like receptor;    peptide;    gold nanoparticle;    trained immunity;   

DOI  :  10.3389/fimmu.2021.750128

来源: DOAJ

【 摘 要 】

Macrophages play an important role in the initiation, progression and resolution of inflammation in many human diseases. Effective regulation of their activation and immune responses could be a promising therapeutic strategy to manage various inflammatory conditions. Nanodevices that naturally target macrophages are ideal agents to regulate immune responses of macrophages. Here we described a special tryptophan (Trp)-containing hexapeptide-coated gold nanoparticle hybrid, PW, which had unique immunomodulatory activities on macrophages. The Trp residues enabled PW higher affinity to cell membranes, and contributed to inducing mild pro-inflammatory responses of NF-κB/AP-1 activation. However, in the presence of TLR stimuli, PW exhibited potent anti-inflammatory activities through inhibiting multiple TLR signaling pathways. Mechanistically, PW was internalized primarily through micropinocytosis pathway into macrophages and attenuated the endosomal acidification process, and hence preferentially affected the endosomal TLR signaling. Interestingly, PW could induce the expression of the TLR negative regulator IRAK-M, which may also contribute to the observed TLR inhibitory activities. In two acute lung injury (ALI) mouse models, PW could effectively ameliorate lung inflammation and protect lung from injuries. This work demonstrated that nanodevices with thoughtful design could serve as novel immunomodulatory agents to manage the dysregulated inflammatory responses for treating many chronic and acute inflammatory conditions, such as ALI.

【 授权许可】

Unknown