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Epigenetic regulation of high glucose‐induced proinflammatory cytokine production in monocytes by curcumin
Author(s) -
Yun JungMi,
Jialal Ishwarlal,
Devaraj Sridevi
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1030.9
Subject(s) - proinflammatory cytokine , curcumin , acetylation , chemistry , cytokine , histone , inflammation , endocrinology , immunology , biology , biochemistry , gene
Diabetes is a pro‐inflammatory state. We have shown increased monocyte proinflammatory cytokines in patients with diabetes. High glucose (HG) induces inflammatory cytokines via epigenetic changes. Curcumin is anti‐inflammatory and may regulate chromatin remodeling by inhibiting histone acetylation. In this study, we tested the effect of curcumin on histone acetylation and inflammatory cytokine secretion under HG conditions in monocytes. THP‐1 cells were cultured in presence of normal glucose (NG, 5.5 mmol/L) or HG(25 mmol/L) conditions in absence or presence of curcumin (1.5–12.5μM) for 72h. Cytokine level, NFκB transactivation, histone deacetylases (HDACs) activity, and histone acetylases (HATs) activity were measured by immunoblotting, ELISA and immunofluorescence. HG activates HAT which in turn acetylates p65 and suppresses HDAC2 resulting in NFκB activation and increased transcription of IL‐6 and TNF‐α in monocytes. Curcumin induces HDAC2 and decreases HAT (p300) activity, thereby resulting in decreased NFκB activation and decreased inflammatory cytokine release (p<0.001) in HG conditions. These results indicate that curcumin decreases HG‐induced cytokine production in monocytes via epigenetic changes involving NFκB. In conclusion, curcumin supplementation by reducing vascular inflammation may prevent diabetic complications. Grant Funding Source : N / A