Epigallocatechin-3-gallate inhibits interleukin-1β-induced expression of nitric oxide synthase and production of nitric oxide in human chondrocytes. Suppression of nuclear factor κB by degradation of the inhibitor of nuclear factor κB
Bibliographic record
Abstract
Objective. The proinflammatory cytokine interleukin-1 (IL-1 ) induces the production of high levels of nitric oxide (NO) in human chondrocytes. Green tea (Camellia sinensis) polyphenols are potent antiinflammatory agents and have been shown to inhibit NO production in tumor cell lines. In the present study, we examined the effect of epigallocatechin-3-gallate (EGCG), a green tea polyphenol, on IL-1 –induced production of NO in primary human osteoarthritis (OA) chondrocytes. Methods. Human chondrocytes were derived from OA cartilage and were treated with EGCG (100 M) and IL-1 (2 ng/ml) for different periods, and inducible nitric oxide synthase (iNOS) messenger RNA and protein expression was determined by real-time quantitative reverse transcriptase–polymerase chain reaction and Western blotting, respectively. Production of NO was determined as nitrite in culture supernatant. Activation and translocation of nuclear factor B (NFB), levels of inhibitor of nuclear factor B (I B), and NFB DNA binding activity were determined by Western blotting and a highly sensitive and specific enzymelinked immunosorbent assay. Activity of I B kinase was determined using in vitro kinase assay. Results. Human chondrocytes cotreated with EGCG produced significantly less NO compared with chondrocytes stimulated with IL-1 alone (P < 0.005). The inhibition of NO production correlated with the suppression of induction and expression of NFB– dependent gene iNOS. EGCG inhibited the activation and translocation of NFB to the nucleus by suppressing the degradation of its inhibitory protein I B in the cytoplasm. Conclusion. Our results indicate that EGCG inhibits the IL-1 –induced production of NO in human chondrocytes by interfering with the activation of NFB through a novel mechanism. Our data further suggest that EGCG may be a therapeutically effective inhibitor of IL-1 –induced inflammatory effects that are dependent on NFB activation in human OA chondrocytes.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".