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A wild rice-derived peptide R14 ameliorates monosodium urate crystals-induced IL-1β secretion through inhibition of NF-κB signaling and NLRP3 inflammasome activation.

ABSTRACT: Gout is an inflammatory arthritis initiated by the deposition of monosodium urate crystals (MSU) around the joints and surrounding tissues. MSU crystals activate the nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome to the release of interleukin-1β (IL-1β). Gout can have a substantial impact on patient's quality of life, and currently available medicines are unable to meet all the clinical needs. This study explored anti-gout potentials of the Rice14 (R14) peptide, a peptide derived from leaves of wild rice Oryza minuta. The effects of R14 peptide on IL-1β secretion in THP-1 macrophages with MSU crystals-induced inflammation were examined. Our results clearly showed that the R14 peptide significantly inhibited the secretion of IL-1β in MSU crystals-induced macrophages, and the effects were dose-related. For safety testing, the R14 peptide did not show both cytotoxicity and hemolytic activity. In addition, the R14 peptide strongly suppressed the phospho-IκB-α and nuclear factor kappa-B (NF-κB) p65 proteins in NF-κB signaling pathway, reduced the NLRP3 expression and inhibited the MSU crystals-mediated cleavage of caspase-1 as well as mature IL-1β. The R14 peptide also reduced MSU-triggered intracellular ROS levels in macrophages. Taken together, these results indicated that R14 peptide inhibited MSU crystals-induced IL-1β production through NF-κB and NLRP3 inflammasome activation. Our findings demonstrated that R14 peptide, the newly recognized peptide from wild rice, possessed potent regulatory activity against IL-1β production in MSU crystals-induced inflammation, and we therefore propose that the R14 peptide is a promising molecule with potential clinical application in the treatment of MSU crystals-induced inflammation.

SUBMITTER: Charoenwutthikun S

PROVIDER: S-EPMC10184658 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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A wild rice-derived peptide R14 ameliorates monosodium urate crystals-induced IL-1β secretion through inhibition of NF-κB signaling and NLRP3 inflammasome activation.

Charoenwutthikun Supattra S Chanjitwiriya Kasem K Roytrakul Sittiruk S Kunthalert Duangkamol D

PeerJ 20230512

Gout is an inflammatory arthritis initiated by the deposition of monosodium urate crystals (MSU) around the joints and surrounding tissues. MSU crystals activate the nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome to the release of interleukin-1β (IL-1β). Gout can have a substantial impact on patient's quality of life, and currently available medicines are unable to meet all the clinical needs. This study explored anti-gout potentials of the ...[more]

PMID: 37197585

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Project description:Diabetic nephropathy (DN) as the primary cause of end-stage kidney disease is a common complication of diabetes. Recent researches have shown the activation of nuclear factor kappa light-chain enhancer of activated B cells (NF-κB) and NACHT, LRR and PYD domain-containing protein 3 (NLRP3) inflammasome are associated with inflammation in the progression of DN, but the exact mechanism is unclear. Long noncoding RNAs (lncRNAs) have roles in the development of many diseases including DN. However, the relationship between lncRNAs and inflammation in DN remains largely unknown. Our previous study has revealed that 14 lncRNAs are abnormally expressed in DN by RNA sequencing and real-time quantitative PCR (qRT-PCR) in the renal tissues of db/db DN mice. In this study, these lncRNAs were verified their expressions by qRT-PCR in mesangial cells (MCs) cultured under high- and low-glucose conditions. Twelve lncRNAs displayed the same expressional tendencies in both renal tissues and MCs. In particular, long intergenic noncoding RNA (lincRNA)-Gm4419 was the only one associating with NF-κB among these 12 lncRNAs by bioinformatics methods. Moreover, Gm4419 knockdown could obviously inhibit the expressions of pro-inflammatory cytokines and renal fibrosis biomarkers, and reduce cell proliferation in MCs under high-glucose condition, whereas overexpression of Gm4419 could increase the inflammation, fibrosis and cell proliferation in MCs under low-glucose condition. Interestingly, our results showed that Gm4419 could activate the NF-κB pathway by directly interacting with p50, the subunit of NF-κB. In addition, we found that p50 could interact with NLRP3 inflammasome in MCs. In conclusion, our findings suggest lincRNA-Gm4419 may participate in the inflammation, fibrosis and proliferation in MCs under high-glucose condition through NF-κB/NLRP3 inflammasome signaling pathway, and may provide new insights into the regulation of Gm4419 during the progression of DN.

Dataset Information

A wild rice-derived peptide R14 ameliorates monosodium urate crystals-induced IL-1β secretion through inhibition of NF-κB signaling and NLRP3 inflammasome activation.

Publications

A wild rice-derived peptide R14 ameliorates monosodium urate crystals-induced IL-1β secretion through inhibition of NF-κB signaling and NLRP3 inflammasome activation.

Similar Datasets

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