Octominin Inhibits LPS-Induced Chemokine and Pro-inflammatory Cytokine Secretion from RAW 264.7 Macrophages via Blocking TLRs/NF-κB Signal Transduction.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101596414 Publication Model: Electronic Cited Medium: Internet ISSN: 2218-273X (Electronic) Linking ISSN: 2218273X NLM ISO Abbreviation: Biomolecules Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, 2011-

Anti-Inflammatory Agents, Non-Steroidal/*pharmacology ; Antimicrobial Cationic Peptides/*pharmacology ; Cytokines/*metabolism ; Octopodiformes/*chemistry ; Peptide Fragments/*pharmacology ; Peptides/*pharmacology ; Signal Transduction/*drug effects; Animals ; Chemokines/genetics ; Chemokines/metabolism ; Cytokines/genetics ; Dinoprostone/metabolism ; Inflammation Mediators/metabolism ; Lipopolysaccharides/pharmacology ; Lymphocyte Antigen 96/chemistry ; Lymphocyte Antigen 96/metabolism ; Macrophages/drug effects ; Macrophages/metabolism ; Mice ; NF-kappa B/metabolism ; Nitric Oxide/metabolism ; Nitric Oxide Synthase Type II/metabolism ; Peptides/genetics ; Phosphorylation/drug effects ; RAW 264.7 Cells ; Toll-Like Receptor 4/classification ; Toll-Like Receptor 4/metabolism

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.
Competing Interests: The authors declare no conflict of interest.

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MABIK2020M00600 and 2019R1A2C1087028 International This work was supported by the Research Program of the National Marine Biodiversity Institute of Korea (MABIK2020M00600) funded by the Ministry of Oceans and Fisheries and by the National Research Foundation of Korea (NRF) grant funded by the Korea govern

Keywords: NF-κB; Octopus minor; RAW 264.7; chemokines; inflammation; peptide

0 (Anti-Inflammatory Agents, Non-Steroidal)
0 (Antimicrobial Cationic Peptides)
0 (Chemokines)
0 (Cytokines)
0 (Inflammation Mediators)
0 (Lipopolysaccharides)
0 (Ly96 protein, mouse)
0 (Lymphocyte Antigen 96)
0 (NF-kappa B)
0 (Peptide Fragments)
0 (Peptides)
0 (Tlr4 protein, mouse)
0 (Toll-Like Receptor 4)
0 (octominin)
31C4KY9ESH (Nitric Oxide)
EC 1.14.13.39 (Nitric Oxide Synthase Type II)
EC 1.14.13.39 (Nos2 protein, mouse)
K7Q1JQR04M (Dinoprostone)

Date Created: 20200402 Date Completed: 20210415 Latest Revision: 20240328

20240329

PMC7226457

10.3390/biom10040511

32230927