Antimicrobial Peptide LL-37 Drives Rosacea-Like Skin Inflammation in an NLRP3-Dependent Manner

Yoon, Sung-Hyun; Hwang, Inhwa; Lee, Eunju; Cho, Hyo-Joung; Ryu, Jee Hoon; Kim, Tae Kyun; Yu, Jeong Sik

doi:10.1016/j.jid.2021.02.745

Cited by 36 publications

(29 citation statements)

References 39 publications

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“…Among them, MCC950, a sulfonylurea molecule, exhibits specificity in inhibiting the NLRP3 inflammasome, reducing IL-1β release and apoptosis without affecting other signaling pathways ( Coll et al, 2019 ). Numerous studies have demonstrated that MCC950 has a good anti-inflammatory effect in various inflammatory diseases, such as cryopyrin-related syndrome, lung inflammation, renal fibrosis, hypertension, and myocardial infarction ( Gao et al, 2019 ; Krishnan et al, 2019 ; Corcoran et al, 2021 ; Wang L. et al, 2021 ; Yoon et al, 2021 ). However, as far as we know, DED treatments using MCC950 have been seldom reported.…”

Section: Introductionmentioning

confidence: 99%

Mussel-Inspired Microgel Encapsulated NLRP3 Inhibitor as a Synergistic Strategy Against Dry Eye

Zha

Chen

Xiao

et al. 2022

Front. Bioeng. Biotechnol.

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The inflammatory response mediated by oxidative stress is the main pathogenesis of dry eye, but clinical observations have shown that scavenging oxygen-free radicals alone has limited therapeutic effect. Moreover, the unique anatomy and physiology of the ocular surface result in low bioavailability of drugs, and higher concentration is required to achieve the desired efficacy, which, however, may bring systemic side effects. These problems pose a challenge, but the revelation of the ROS-NLRP3-IL-1β signaling axis opens up new possibilities. In this investigation, an NLRP3 inhibitor was successfully encapsulated in polydopamine-based microgels and used for dry eye treatment. It was demonstrated that the well-designed microgels exhibited good biocompatibility, prolonged drug retention time on the ocular surface, and effective inhibition of corneal epithelial damage and cell apoptosis. In addition, due to the synergistic effect, the NLRP3 inhibitor–loaded microgels could exert enhanced oxygen radical scavenging and inflammation-inhibiting effects at a lower dose than monotherapy. These findings suggest that polydopamine-based microgels have advantages as ocular surface drug delivery platforms and have promising applications in oxidative damage–related inflammatory diseases in synergy with anti-inflammatory drugs.

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Section: Introductionmentioning

confidence: 99%

Mussel-Inspired Microgel Encapsulated NLRP3 Inhibitor as a Synergistic Strategy Against Dry Eye

Zha

Chen

Xiao

et al. 2022

Front. Bioeng. Biotechnol.

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“…Previous work has shown that the antimicrobial peptide LL-37/cathelicidin activates the inflammasome pathway [ 21 , 33 ]. LL-37 and HRPs are similar to the extent that they are able to interfere with microbial membranes inducing lysis of bacteria.…”

Section: Resultsmentioning

confidence: 99%

Efficient Induction of Antigen-Specific CD8+ T-Cell Responses by Cationic Peptide-Based mRNA Nanoparticles

et al. 2022

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A major determinant for the success of mRNA-based vaccines is the composition of the nanoparticles (NPs) used for formulation and delivery. Cationic peptides represent interesting candidate carriers for mRNA, since they have been shown to efficiently deliver nucleic acids to eukaryotic cells. mRNA NPs based on arginine-rich peptides have previously been demonstrated to induce potent antigen-specific CD8+ T-cell responses. We therefore compared the histidine-rich amphipathic peptide LAH4-L1 (KKALLAHALHLLALLALHLAHALKKA) to the fully substituted arginine variant (LAH4-L1R) for their capacity to formulate mRNA and transfect dendritic cells (DCs). Although both peptides encapsulated mRNA to the same extent, and showed excellent uptake in DCs, the gene expression level was significantly higher for LAH4-L1. The LAH4-L1–mRNA NPs also resulted in enhanced antigen presentation in the context of MHC I compared to LAH4-L1R in primary murine CD103+ DCs. Both peptides induced DC maturation and inflammasome activation. Subsequent ex vivo stimulation of OT-I splenocytes with transfected CD103+ DCs resulted in a high proportion of polyfunctional CD8+ T cells for both peptides. In addition, in vivo immunization with LAH4-L1 or LAH4-L1R–mRNA NPs resulted in proliferation of antigen-specific T cells. In conclusion, although LAH4-L1 outperformed LAH4-L1R in terms of transfection efficiency, the immune stimulation ex vivo and in vivo was equally efficient.

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“…Research on the immunology related to the rosacea pathogenesis has rapidly increased in recent years. In addition to the technologies, research models have been established to aid this effort (LL-37 induced rosacea-like traits in mice and various cells) [ 55 ]. LL-37 (Cathelicidin antimicrobial peptide) and kallikrein 5 (KLK5) may serve as the key contributors to the proinflammatory and proangiogenic effects, which are highly expressed in the skin of patients with rosacea.…”

Section: Discussionmentioning

confidence: 99%

Current research and clinical trends in rosacea pathogenesis

Hu¹,

Li²,

Zhang³

et al. 2022

Heliyon

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Antimicrobial Peptide LL-37 Drives Rosacea-Like Skin Inflammation in an NLRP3-Dependent Manner

Cited by 36 publications

References 39 publications

Mussel-Inspired Microgel Encapsulated NLRP3 Inhibitor as a Synergistic Strategy Against Dry Eye

Mussel-Inspired Microgel Encapsulated NLRP3 Inhibitor as a Synergistic Strategy Against Dry Eye

Efficient Induction of Antigen-Specific CD8+ T-Cell Responses by Cationic Peptide-Based mRNA Nanoparticles

Current research and clinical trends in rosacea pathogenesis

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