Inhibition of inflammatory cell infiltration by antagonistic peptides that specifically bind to CCR5 via regulation of the NF-kB signaling pathway in rats with colitis
Introduction CC chemokine receptor 5 (CCR5) and the NF-kB signaling pathway play important roles in the pathophysiology of inflammatory bowel disease (IBD). Previously, we synthesized two peptides (GH and HY peptides) that specifically bind to the first and the second extracellular loops (ECL1 and E...
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Termedia Publishing House
2021-05-01
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| Series: | Archives of Medical Science |
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| Online Access: | https://www.archivesofmedicalscience.com/Inhibition-of-inflammatory-cell-infiltration-by-antagonistic-peptides-that-specifically,127587,0,2.html |
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| author | Yang-Da Song Yi-Hang Song Si-Xue Liu Hua-Rong Huang Ying-Qiang Zhong |
| author_facet | Yang-Da Song Yi-Hang Song Si-Xue Liu Hua-Rong Huang Ying-Qiang Zhong |
| author_sort | Yang-Da Song |
| collection | DOAJ |
| description | Introduction
CC chemokine receptor 5 (CCR5) and the NF-kB signaling pathway play important roles in the pathophysiology of inflammatory bowel disease (IBD). Previously, we synthesized two peptides (GH and HY peptides) that specifically bind to the first and the second extracellular loops (ECL1 and ECL2, respectively) of CCR5 and preliminarily found an inhibitory effect of these peptides on colitis. However, the specific mechanism by which these two peptides regulate trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats remains unclear. Aim of the study was to further investigate the effect and mechanism of CCR5 binding peptides in rat colitis.
Material and methods
Experimental colitis was induced by 5% TNBS. CCR5 antagonist peptides were administered intravenously once a day for a week. Histological evaluation, real-time PCR, western blotting and correlation analysis were performed to examine the effects of the CCR5 binding peptides on the infiltration of inflammatory cells and the NF-kB signaling pathway.
Results
Administration of GH and HY peptides ameliorated mucosal damage and reduced the infiltration of neutrophils, lymphocytes and macrophages in experimental colitis (p < 0.05). The expression of NF-kB-related genes, including p105, p100, IKK and TNF-α, was reduced after GH and HY peptide administration (p < 0.01), and the protein level of TNF-α and the phosphorylation of IKK, IkBα and p65 were also suppressed. Furthermore, the CCR5 antagonist peptides inhibited nuclear translocation of p65. Spearman correlation analysis showed that the infiltration of inflammatory cells was significantly correlated with the NF-kB pathway.
Conclusions
Antagonistic peptides that specifically bind to ECL1 and ECL2 of CCR5 inhibit the infiltration of neutrophils, lymphocytes and macrophages in the colonic mucosa of SD rats with TNBS-induced colitis via regulation of the NF-κB signaling pathway. |
| format | Article |
| id | doaj-art-63741c2ebecb4ed5bb025d97226a911a |
| institution | Kabale University |
| issn | 1734-1922 1896-9151 |
| language | English |
| publishDate | 2021-05-01 |
| publisher | Termedia Publishing House |
| record_format | Article |
| series | Archives of Medical Science |
| spelling | doaj-art-63741c2ebecb4ed5bb025d97226a911a2025-01-27T10:45:12ZengTermedia Publishing HouseArchives of Medical Science1734-19221896-91512021-05-012062022203310.5114/aoms/127587127587Inhibition of inflammatory cell infiltration by antagonistic peptides that specifically bind to CCR5 via regulation of the NF-kB signaling pathway in rats with colitisYang-Da Song0https://orcid.org/0000-0002-5915-0260Yi-Hang Song1Si-Xue Liu2Hua-Rong Huang3Ying-Qiang Zhong4https://orcid.org/0000-0003-3017-2965Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, ChinaDepartment of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, ChinaDepartment of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, ChinaKey Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes of Sun Yat-Sen University, Guangzhou, ChinaDepartment of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, ChinaIntroduction CC chemokine receptor 5 (CCR5) and the NF-kB signaling pathway play important roles in the pathophysiology of inflammatory bowel disease (IBD). Previously, we synthesized two peptides (GH and HY peptides) that specifically bind to the first and the second extracellular loops (ECL1 and ECL2, respectively) of CCR5 and preliminarily found an inhibitory effect of these peptides on colitis. However, the specific mechanism by which these two peptides regulate trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats remains unclear. Aim of the study was to further investigate the effect and mechanism of CCR5 binding peptides in rat colitis. Material and methods Experimental colitis was induced by 5% TNBS. CCR5 antagonist peptides were administered intravenously once a day for a week. Histological evaluation, real-time PCR, western blotting and correlation analysis were performed to examine the effects of the CCR5 binding peptides on the infiltration of inflammatory cells and the NF-kB signaling pathway. Results Administration of GH and HY peptides ameliorated mucosal damage and reduced the infiltration of neutrophils, lymphocytes and macrophages in experimental colitis (p < 0.05). The expression of NF-kB-related genes, including p105, p100, IKK and TNF-α, was reduced after GH and HY peptide administration (p < 0.01), and the protein level of TNF-α and the phosphorylation of IKK, IkBα and p65 were also suppressed. Furthermore, the CCR5 antagonist peptides inhibited nuclear translocation of p65. Spearman correlation analysis showed that the infiltration of inflammatory cells was significantly correlated with the NF-kB pathway. Conclusions Antagonistic peptides that specifically bind to ECL1 and ECL2 of CCR5 inhibit the infiltration of neutrophils, lymphocytes and macrophages in the colonic mucosa of SD rats with TNBS-induced colitis via regulation of the NF-κB signaling pathway.https://www.archivesofmedicalscience.com/Inhibition-of-inflammatory-cell-infiltration-by-antagonistic-peptides-that-specifically,127587,0,2.htmlinflammatory bowel diseasecc chemokine receptor 5antagonistic peptidesnf-kb |
| spellingShingle | Yang-Da Song Yi-Hang Song Si-Xue Liu Hua-Rong Huang Ying-Qiang Zhong Inhibition of inflammatory cell infiltration by antagonistic peptides that specifically bind to CCR5 via regulation of the NF-kB signaling pathway in rats with colitis Archives of Medical Science inflammatory bowel disease cc chemokine receptor 5 antagonistic peptides nf-kb |
| title | Inhibition of inflammatory cell infiltration by antagonistic peptides that specifically bind to CCR5 via regulation of the NF-kB signaling pathway in rats with colitis |
| title_full | Inhibition of inflammatory cell infiltration by antagonistic peptides that specifically bind to CCR5 via regulation of the NF-kB signaling pathway in rats with colitis |
| title_fullStr | Inhibition of inflammatory cell infiltration by antagonistic peptides that specifically bind to CCR5 via regulation of the NF-kB signaling pathway in rats with colitis |
| title_full_unstemmed | Inhibition of inflammatory cell infiltration by antagonistic peptides that specifically bind to CCR5 via regulation of the NF-kB signaling pathway in rats with colitis |
| title_short | Inhibition of inflammatory cell infiltration by antagonistic peptides that specifically bind to CCR5 via regulation of the NF-kB signaling pathway in rats with colitis |
| title_sort | inhibition of inflammatory cell infiltration by antagonistic peptides that specifically bind to ccr5 via regulation of the nf kb signaling pathway in rats with colitis |
| topic | inflammatory bowel disease cc chemokine receptor 5 antagonistic peptides nf-kb |
| url | https://www.archivesofmedicalscience.com/Inhibition-of-inflammatory-cell-infiltration-by-antagonistic-peptides-that-specifically,127587,0,2.html |
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