Cargando…
A novel modified-curcumin 2.24 resolves inflammation by promoting M2 macrophage polarization
To assess resolving-like activity by a novel chemically-modified curcumin (CMC2.24) in a “two-hit” model of diabetes-associated periodontitis. Macrophages from rats were cultured in the presence/absence of either Lipopolysaccharide (LPS, 1st hit); or advanced-glycation-end products (AGE, 2nd hit); o...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10509274/ https://www.ncbi.nlm.nih.gov/pubmed/37726411 http://dx.doi.org/10.1038/s41598-023-42848-x |
_version_ | 1785107709351165952 |
---|---|
author | Deng, Jie Golub, Lorne M. Lee, Hsi-Ming Bhatt, Heta-Dinesh Johnson, Francis Xu, Tian-min Gu, Ying |
author_facet | Deng, Jie Golub, Lorne M. Lee, Hsi-Ming Bhatt, Heta-Dinesh Johnson, Francis Xu, Tian-min Gu, Ying |
author_sort | Deng, Jie |
collection | PubMed |
description | To assess resolving-like activity by a novel chemically-modified curcumin (CMC2.24) in a “two-hit” model of diabetes-associated periodontitis. Macrophages from rats were cultured in the presence/absence of either Lipopolysaccharide (LPS, 1st hit); or advanced-glycation-end products (AGE, 2nd hit); or both combined. CMC2.24 was added as treatment. The conditioned media were analyzed for MMP-9, cytokines (IL-1β, IL-6, TNF-α), resolvins (RvD(1), RvE(1), lipoxin A(4)), and soluble receptor for AGE (sRAGE). The phenotypes of M1/M2 macrophage were analyzed by flow cytometry. Both LPS/AGE-alone, and two-combined, dramatically increased the secretion of MMP-9 by macrophages. CMC2.24 “normalized” the elevated levels of MMP-9 under all conditions. Moreover, CMC2.24 significantly reduced the secretion of IL-1β and IL-6 with a fewer effects on TNF-α. Importantly, CMC2.24 increased RvD(1) and sRAGE secretion by macrophages exposed to LPS/AGE; and both treatment groups exhibited increased M2 relative to M1 populations. Furthermore, scatter-diagram showed the macrophages gradually shifted from M1 towards M2 with CMC2.24-treated, whereas LPS/AGE-alone groups remained unchanged. CMC2.24 “normalized” cytokines and MMP-9, but also enhanced RvD(1) and sRAGE in macrophages. Crucially, CMC2.24 appears to be a potent inhibitor of the pro-inflammatory M1 phenotype; and a promotor of the pro-resolving M2 phenotype, thus acting like a crucial “switch” to reduce inflammation. |
format | Online Article Text |
id | pubmed-10509274 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-105092742023-09-21 A novel modified-curcumin 2.24 resolves inflammation by promoting M2 macrophage polarization Deng, Jie Golub, Lorne M. Lee, Hsi-Ming Bhatt, Heta-Dinesh Johnson, Francis Xu, Tian-min Gu, Ying Sci Rep Article To assess resolving-like activity by a novel chemically-modified curcumin (CMC2.24) in a “two-hit” model of diabetes-associated periodontitis. Macrophages from rats were cultured in the presence/absence of either Lipopolysaccharide (LPS, 1st hit); or advanced-glycation-end products (AGE, 2nd hit); or both combined. CMC2.24 was added as treatment. The conditioned media were analyzed for MMP-9, cytokines (IL-1β, IL-6, TNF-α), resolvins (RvD(1), RvE(1), lipoxin A(4)), and soluble receptor for AGE (sRAGE). The phenotypes of M1/M2 macrophage were analyzed by flow cytometry. Both LPS/AGE-alone, and two-combined, dramatically increased the secretion of MMP-9 by macrophages. CMC2.24 “normalized” the elevated levels of MMP-9 under all conditions. Moreover, CMC2.24 significantly reduced the secretion of IL-1β and IL-6 with a fewer effects on TNF-α. Importantly, CMC2.24 increased RvD(1) and sRAGE secretion by macrophages exposed to LPS/AGE; and both treatment groups exhibited increased M2 relative to M1 populations. Furthermore, scatter-diagram showed the macrophages gradually shifted from M1 towards M2 with CMC2.24-treated, whereas LPS/AGE-alone groups remained unchanged. CMC2.24 “normalized” cytokines and MMP-9, but also enhanced RvD(1) and sRAGE in macrophages. Crucially, CMC2.24 appears to be a potent inhibitor of the pro-inflammatory M1 phenotype; and a promotor of the pro-resolving M2 phenotype, thus acting like a crucial “switch” to reduce inflammation. Nature Publishing Group UK 2023-09-19 /pmc/articles/PMC10509274/ /pubmed/37726411 http://dx.doi.org/10.1038/s41598-023-42848-x Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Deng, Jie Golub, Lorne M. Lee, Hsi-Ming Bhatt, Heta-Dinesh Johnson, Francis Xu, Tian-min Gu, Ying A novel modified-curcumin 2.24 resolves inflammation by promoting M2 macrophage polarization |
title | A novel modified-curcumin 2.24 resolves inflammation by promoting M2 macrophage polarization |
title_full | A novel modified-curcumin 2.24 resolves inflammation by promoting M2 macrophage polarization |
title_fullStr | A novel modified-curcumin 2.24 resolves inflammation by promoting M2 macrophage polarization |
title_full_unstemmed | A novel modified-curcumin 2.24 resolves inflammation by promoting M2 macrophage polarization |
title_short | A novel modified-curcumin 2.24 resolves inflammation by promoting M2 macrophage polarization |
title_sort | novel modified-curcumin 2.24 resolves inflammation by promoting m2 macrophage polarization |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10509274/ https://www.ncbi.nlm.nih.gov/pubmed/37726411 http://dx.doi.org/10.1038/s41598-023-42848-x |
work_keys_str_mv | AT dengjie anovelmodifiedcurcumin224resolvesinflammationbypromotingm2macrophagepolarization AT golublornem anovelmodifiedcurcumin224resolvesinflammationbypromotingm2macrophagepolarization AT leehsiming anovelmodifiedcurcumin224resolvesinflammationbypromotingm2macrophagepolarization AT bhatthetadinesh anovelmodifiedcurcumin224resolvesinflammationbypromotingm2macrophagepolarization AT johnsonfrancis anovelmodifiedcurcumin224resolvesinflammationbypromotingm2macrophagepolarization AT xutianmin anovelmodifiedcurcumin224resolvesinflammationbypromotingm2macrophagepolarization AT guying anovelmodifiedcurcumin224resolvesinflammationbypromotingm2macrophagepolarization AT dengjie novelmodifiedcurcumin224resolvesinflammationbypromotingm2macrophagepolarization AT golublornem novelmodifiedcurcumin224resolvesinflammationbypromotingm2macrophagepolarization AT leehsiming novelmodifiedcurcumin224resolvesinflammationbypromotingm2macrophagepolarization AT bhatthetadinesh novelmodifiedcurcumin224resolvesinflammationbypromotingm2macrophagepolarization AT johnsonfrancis novelmodifiedcurcumin224resolvesinflammationbypromotingm2macrophagepolarization AT xutianmin novelmodifiedcurcumin224resolvesinflammationbypromotingm2macrophagepolarization AT guying novelmodifiedcurcumin224resolvesinflammationbypromotingm2macrophagepolarization |