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

Journal Article · Tue Aug 15 04:00:00 EDT 2017 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/J.TAAP.2017.05.016· OSTI ID:22722892

Fechtner, Sabrina; Singh, Anil ^[1]; Chourasia, Mukesh ^[2]; Ahmed, Salahuddin ^[1]

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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)

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.

• OSTI ID: 22722892
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Vol. 329; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
BEVERAGES
FIBROBLASTS
INHIBITION
PHOSPHORUS 38
RHEUMATIC DISEASES
SIGNALS