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Title: Molecular insights into the differences in anti-inflammatory activities of green tea catechins on IL-1β signaling in rheumatoid arthritis synovial fibroblasts

Abstract

In this study, we found that catechins found in green tea (EGCG, EGC, and EC) differentially interfere with the IL-1β signaling pathway which regulates the expression of pro-inflammatory mediators (IL-6 and IL-8) and Cox-2 in primary human rheumatoid arthritis synovial fibroblasts (RASFs). EGCG and EGC inhibited IL-6, IL-8, and MMP-2 production and selectively inhibited Cox-2 expression. EC did not exhibit any inhibitory effects. When we looked at the expression of key signaling proteins in the IL-1β signaling pathway, we found all the tested catechins could inhibit TAK-1 activity. Therefore, the consumption of green tea offers an overall anti-inflammatory effect. Molecular docking analysis confirms that EGCG, EGC, and EC all occupy the active site of the TAK1 kinase domain. However, EGCG occupies the majority of the TAK1 active site. In addition to TAK1 inhibition, EGCG can also inhibit P38 and nuclear NF-κB expression whereas EC and EGC were not effective inhibitors. Our findings suggest one of the main health benefits associated with the consumption of green tea are due to the activity of EGCG and EGC which are both present at higher amounts. Although EGCG is the most effective catechin at inhibiting downstream inflammatory signaling, its effectiveness could be hindered bymore » the presence of EC. Therefore, varying EC content in green tea may reduce the anti-inflammatory effects of other potential catechins in green tea. - Highlights: • Catechins EC and EGC have anti-inflammatory properties in synovial fibroblasts. • EGCG is more effective at inhibiting downstream IL-1β signaling than EGC and EC. • EC content may modify green tea's anti-inflammatory effect by competing with EGCG.« less

Authors:
;  [1];  [2];  [1]
  1. Department of Pharmaceutical Sciences, Washington State University College of Pharmacy, Spokane, WA (United States)
  2. Department of Pharmacoinformatics, National lnstitute of Pharmaceutical Education and Research, Hajipur, Bihar (India)
Publication Date:
OSTI Identifier:
22722892
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 329; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BEVERAGES; FIBROBLASTS; INHIBITION; PHOSPHORUS 38; RHEUMATIC DISEASES; SIGNALS

Citation Formats

Fechtner, Sabrina, Singh, Anil, Chourasia, Mukesh, and Ahmed, Salahuddin. Molecular insights into the differences in anti-inflammatory activities of green tea catechins on IL-1β signaling in rheumatoid arthritis synovial fibroblasts. United States: N. p., 2017. Web. doi:10.1016/J.TAAP.2017.05.016.
Fechtner, Sabrina, Singh, Anil, Chourasia, Mukesh, & Ahmed, Salahuddin. Molecular insights into the differences in anti-inflammatory activities of green tea catechins on IL-1β signaling in rheumatoid arthritis synovial fibroblasts. United States. doi:10.1016/J.TAAP.2017.05.016.
Fechtner, Sabrina, Singh, Anil, Chourasia, Mukesh, and Ahmed, Salahuddin. Tue . "Molecular insights into the differences in anti-inflammatory activities of green tea catechins on IL-1β signaling in rheumatoid arthritis synovial fibroblasts". United States. doi:10.1016/J.TAAP.2017.05.016.
@article{osti_22722892,
title = {Molecular insights into the differences in anti-inflammatory activities of green tea catechins on IL-1β signaling in rheumatoid arthritis synovial fibroblasts},
author = {Fechtner, Sabrina and Singh, Anil and Chourasia, Mukesh and Ahmed, Salahuddin},
abstractNote = {In this study, we found that catechins found in green tea (EGCG, EGC, and EC) differentially interfere with the IL-1β signaling pathway which regulates the expression of pro-inflammatory mediators (IL-6 and IL-8) and Cox-2 in primary human rheumatoid arthritis synovial fibroblasts (RASFs). EGCG and EGC inhibited IL-6, IL-8, and MMP-2 production and selectively inhibited Cox-2 expression. EC did not exhibit any inhibitory effects. When we looked at the expression of key signaling proteins in the IL-1β signaling pathway, we found all the tested catechins could inhibit TAK-1 activity. Therefore, the consumption of green tea offers an overall anti-inflammatory effect. Molecular docking analysis confirms that EGCG, EGC, and EC all occupy the active site of the TAK1 kinase domain. However, EGCG occupies the majority of the TAK1 active site. In addition to TAK1 inhibition, EGCG can also inhibit P38 and nuclear NF-κB expression whereas EC and EGC were not effective inhibitors. Our findings suggest one of the main health benefits associated with the consumption of green tea are due to the activity of EGCG and EGC which are both present at higher amounts. Although EGCG is the most effective catechin at inhibiting downstream inflammatory signaling, its effectiveness could be hindered by the presence of EC. Therefore, varying EC content in green tea may reduce the anti-inflammatory effects of other potential catechins in green tea. - Highlights: • Catechins EC and EGC have anti-inflammatory properties in synovial fibroblasts. • EGCG is more effective at inhibiting downstream IL-1β signaling than EGC and EC. • EC content may modify green tea's anti-inflammatory effect by competing with EGCG.},
doi = {10.1016/J.TAAP.2017.05.016},
journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = ,
volume = 329,
place = {United States},
year = {2017},
month = {8}
}