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Octominin Inhibits LPS-Induced Chemokine and Pro-inflammatory Cytokine Secretion from RAW 264.7 Macrophages via Blocking TLRs/NF-κB Signal Transduction
Inflammation is a well-organized innate immune response that plays an important role during the pathogen attacks and mechanical injuries. The Toll-like receptors (TLR)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a major signal transduction pathway observed in RAW 264.7...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226457/ https://www.ncbi.nlm.nih.gov/pubmed/32230927 http://dx.doi.org/10.3390/biom10040511 |
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author | Sanjeewa, K. K. Asanka Nagahawatta, D. P. Yang, Hye-Won Oh, Jae Young Jayawardena, Thilina U. Jeon, You-Jin De Zoysa, Mahanama Whang, Ilson Ryu, Bomi |
author_facet | Sanjeewa, K. K. Asanka Nagahawatta, D. P. Yang, Hye-Won Oh, Jae Young Jayawardena, Thilina U. Jeon, You-Jin De Zoysa, Mahanama Whang, Ilson Ryu, Bomi |
author_sort | Sanjeewa, K. K. Asanka |
collection | PubMed |
description | Inflammation is a well-organized innate immune response that plays an important role during the pathogen attacks and mechanical injuries. The Toll-like receptors (TLR)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a major signal transduction pathway observed in RAW 264.7 macrophages during the inflammatory responses. Here, we investigated the anti-inflammatory effects of Octominin; a bio-active peptide developed from Octopus minor in RAW 264.7 macrophages in vitro. Octominin was found to inhibit lipopolysaccharides (LPS)-stimulated transcriptional activation of NF-κB in RAW 264.7 cells and dose-dependently decreased the mRNA expression levels of TLR4. Specifically, in silico docking results demonstrated that Octominin has a potential to inhibit TLR4 mediated inflammatory responses via blocking formation of TLR4/MD-2/LPS complex. We also demonstrated that Octominin could significantly inhibit LPS-induced secretion of pro-inflammatory cytokine (interleukin-β; IL-1β, IL-6, and tumor necrosis factor-α) and chemokines (CCL3, CCL4, CCL5, and CXCL10) from RAW 264.7 cells. Additionally, Octominin repressed the LPS-induced pro-inflammatory mediators including nitric oxide (NO), prostaglandin E2, inducible NO synthase, and cyclooxygenase 2 in macrophages. These results suggest that Octominin is a potential inhibitor of TLRs/NF-κB signal transduction pathway and is a potential candidate for the treatment of inflammatory diseases. |
format | Online Article Text |
id | pubmed-7226457 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-72264572020-05-18 Octominin Inhibits LPS-Induced Chemokine and Pro-inflammatory Cytokine Secretion from RAW 264.7 Macrophages via Blocking TLRs/NF-κB Signal Transduction Sanjeewa, K. K. Asanka Nagahawatta, D. P. Yang, Hye-Won Oh, Jae Young Jayawardena, Thilina U. Jeon, You-Jin De Zoysa, Mahanama Whang, Ilson Ryu, Bomi Biomolecules Article Inflammation is a well-organized innate immune response that plays an important role during the pathogen attacks and mechanical injuries. The Toll-like receptors (TLR)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a major signal transduction pathway observed in RAW 264.7 macrophages during the inflammatory responses. Here, we investigated the anti-inflammatory effects of Octominin; a bio-active peptide developed from Octopus minor in RAW 264.7 macrophages in vitro. Octominin was found to inhibit lipopolysaccharides (LPS)-stimulated transcriptional activation of NF-κB in RAW 264.7 cells and dose-dependently decreased the mRNA expression levels of TLR4. Specifically, in silico docking results demonstrated that Octominin has a potential to inhibit TLR4 mediated inflammatory responses via blocking formation of TLR4/MD-2/LPS complex. We also demonstrated that Octominin could significantly inhibit LPS-induced secretion of pro-inflammatory cytokine (interleukin-β; IL-1β, IL-6, and tumor necrosis factor-α) and chemokines (CCL3, CCL4, CCL5, and CXCL10) from RAW 264.7 cells. Additionally, Octominin repressed the LPS-induced pro-inflammatory mediators including nitric oxide (NO), prostaglandin E2, inducible NO synthase, and cyclooxygenase 2 in macrophages. These results suggest that Octominin is a potential inhibitor of TLRs/NF-κB signal transduction pathway and is a potential candidate for the treatment of inflammatory diseases. MDPI 2020-03-27 /pmc/articles/PMC7226457/ /pubmed/32230927 http://dx.doi.org/10.3390/biom10040511 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Sanjeewa, K. K. Asanka Nagahawatta, D. P. Yang, Hye-Won Oh, Jae Young Jayawardena, Thilina U. Jeon, You-Jin De Zoysa, Mahanama Whang, Ilson Ryu, Bomi Octominin Inhibits LPS-Induced Chemokine and Pro-inflammatory Cytokine Secretion from RAW 264.7 Macrophages via Blocking TLRs/NF-κB Signal Transduction |
title | Octominin Inhibits LPS-Induced Chemokine and Pro-inflammatory Cytokine Secretion from RAW 264.7 Macrophages via Blocking TLRs/NF-κB Signal Transduction |
title_full | Octominin Inhibits LPS-Induced Chemokine and Pro-inflammatory Cytokine Secretion from RAW 264.7 Macrophages via Blocking TLRs/NF-κB Signal Transduction |
title_fullStr | Octominin Inhibits LPS-Induced Chemokine and Pro-inflammatory Cytokine Secretion from RAW 264.7 Macrophages via Blocking TLRs/NF-κB Signal Transduction |
title_full_unstemmed | Octominin Inhibits LPS-Induced Chemokine and Pro-inflammatory Cytokine Secretion from RAW 264.7 Macrophages via Blocking TLRs/NF-κB Signal Transduction |
title_short | Octominin Inhibits LPS-Induced Chemokine and Pro-inflammatory Cytokine Secretion from RAW 264.7 Macrophages via Blocking TLRs/NF-κB Signal Transduction |
title_sort | octominin inhibits lps-induced chemokine and pro-inflammatory cytokine secretion from raw 264.7 macrophages via blocking tlrs/nf-κb signal transduction |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226457/ https://www.ncbi.nlm.nih.gov/pubmed/32230927 http://dx.doi.org/10.3390/biom10040511 |
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