The Modulatory Activity of Tryptophan Displaying Nanodevices on Macrophage Activation for Preventing Acute Lung Injury
| Autor: | Rui Wang, Jiameng Gong, Shan-Yu Fung, Liya Sun, Huiqiang Ma, Chenchen Wu, Hong Yang |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Lipopolysaccharides
Male Cell Survival THP-1 Cells Endosome Immunology Metal Nanoparticles Inflammation Lung injury trained immunity Immune system Toll-like receptor immunomodulatory nanoparticles medicine Animals Humans Immunologic Factors Immunology and Allergy Macrophage Micropinocytosis Lung Original Research Chemistry Macrophages Tryptophan Macrophage Activation RC581-607 peptide Interleukin-10 Cell biology Mice Inbred C57BL acute lung injury Liposomes Cytokines Gold Immunologic diseases. Allergy Signal transduction medicine.symptom Peptides Transcriptome Bronchoalveolar Lavage Fluid gold nanoparticle |
| Zdroj: | Frontiers in Immunology, Vol 12 (2021) Frontiers in Immunology |
| ISSN: | 1664-3224 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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