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...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-03-01
|
| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/10/4/511 |
| _version_ | 1797626496736559104 |
|---|---|
| author | K. K. Asanka Sanjeewa D. P. Nagahawatta Hye-Won Yang Jae Young Oh Thilina U. Jayawardena You-Jin Jeon Mahanama De Zoysa Ilson Whang Bomi Ryu |
| author_facet | K. K. Asanka Sanjeewa D. P. Nagahawatta Hye-Won Yang Jae Young Oh Thilina U. Jayawardena You-Jin Jeon Mahanama De Zoysa Ilson Whang Bomi Ryu |
| author_sort | K. K. Asanka Sanjeewa |
| collection | DOAJ |
| 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 <i>Octopus minor</i> 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. |
| first_indexed | 2024-03-11T10:12:11Z |
| format | Article |
| id | doaj.art-ceeaa55e7a24491494a43aa69e9b665c |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-11T10:12:11Z |
| publishDate | 2020-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-ceeaa55e7a24491494a43aa69e9b665c2023-11-16T14:29:42ZengMDPI AGBiomolecules2218-273X2020-03-0110451110.3390/biom10040511Octominin Inhibits LPS-Induced Chemokine and Pro-inflammatory Cytokine Secretion from RAW 264.7 Macrophages via Blocking TLRs/NF-κB Signal TransductionK. K. Asanka Sanjeewa0D. P. Nagahawatta1Hye-Won Yang2Jae Young Oh3Thilina U. Jayawardena4You-Jin Jeon5Mahanama De Zoysa6Ilson Whang7Bomi Ryu8Department of Marine Life Science, Jeju National University, Jeju 63243, KoreaDepartment of Marine Life Science, Jeju National University, Jeju 63243, KoreaDepartment of Marine Life Science, Jeju National University, Jeju 63243, KoreaDepartment of Marine Life Science, Jeju National University, Jeju 63243, KoreaDepartment of Marine Life Science, Jeju National University, Jeju 63243, KoreaDepartment of Marine Life Science, Jeju National University, Jeju 63243, KoreaCollege of Veterinary Medicine, Chungnam National University, Yuseong-gu, Daejeon 34134, KoreaDepartment of Genetic Resources Research, National Marine Biodiversity Institute of Korea (MABIK), Chungchungnam-do 33662, KoreaDepartment of Marine Life Science, Jeju National University, Jeju 63243, KoreaInflammation 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 <i>Octopus minor</i> 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.https://www.mdpi.com/2218-273X/10/4/511<i>Octopus minor</i>peptideinflammationchemokinesRAW 264.7NF-κB |
| spellingShingle | K. K. Asanka Sanjeewa D. P. Nagahawatta Hye-Won Yang Jae Young Oh Thilina U. Jayawardena You-Jin Jeon Mahanama De Zoysa Ilson Whang Bomi Ryu Octominin Inhibits LPS-Induced Chemokine and Pro-inflammatory Cytokine Secretion from RAW 264.7 Macrophages via Blocking TLRs/NF-κB Signal Transduction Biomolecules <i>Octopus minor</i> peptide inflammation chemokines RAW 264.7 NF-κB |
| 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 | <i>Octopus minor</i> peptide inflammation chemokines RAW 264.7 NF-κB |
| url | https://www.mdpi.com/2218-273X/10/4/511 |
| work_keys_str_mv | AT kkasankasanjeewa octominininhibitslpsinducedchemokineandproinflammatorycytokinesecretionfromraw2647macrophagesviablockingtlrsnfkbsignaltransduction AT dpnagahawatta octominininhibitslpsinducedchemokineandproinflammatorycytokinesecretionfromraw2647macrophagesviablockingtlrsnfkbsignaltransduction AT hyewonyang octominininhibitslpsinducedchemokineandproinflammatorycytokinesecretionfromraw2647macrophagesviablockingtlrsnfkbsignaltransduction AT jaeyoungoh octominininhibitslpsinducedchemokineandproinflammatorycytokinesecretionfromraw2647macrophagesviablockingtlrsnfkbsignaltransduction AT thilinaujayawardena octominininhibitslpsinducedchemokineandproinflammatorycytokinesecretionfromraw2647macrophagesviablockingtlrsnfkbsignaltransduction AT youjinjeon octominininhibitslpsinducedchemokineandproinflammatorycytokinesecretionfromraw2647macrophagesviablockingtlrsnfkbsignaltransduction AT mahanamadezoysa octominininhibitslpsinducedchemokineandproinflammatorycytokinesecretionfromraw2647macrophagesviablockingtlrsnfkbsignaltransduction AT ilsonwhang octominininhibitslpsinducedchemokineandproinflammatorycytokinesecretionfromraw2647macrophagesviablockingtlrsnfkbsignaltransduction AT bomiryu octominininhibitslpsinducedchemokineandproinflammatorycytokinesecretionfromraw2647macrophagesviablockingtlrsnfkbsignaltransduction |