title: Transcriptional regulation of cytokines and oxidative stress by gallic acid in human THP-1 monocytes.
abstract: Increased inflammation/prooxidation has been linked not only to Type 2 diabetes but also in prediabetes state. In this study we investigated hyperglycemia-mediated proinflammatory/prooxidant effects in THP-1 monocytes and tested whether gallic acid could attenuate changes in gene expression induced by high-glucose. Cells were treated either with 5.5mM glucose or 25mM glucose in the absence and presence of gallic acid. While oxidative DNA damage was assessed by COMET assay, GSH and GSSG levels were estimated fluorimetrically. Gene expression patterns were determined by RT-PCR. Cells treated with high-glucose showed increased DNA damage and glutathione depletion and this was attenuated in the presence of gallic acid. High-glucose treated cells exhibited increased mRNA expression of TNF-alpha, IL-6, NADPH oxidase and TXNIP and gallic acid attenuated these proinflammatory and prooxidant effects. Cells treated with high-glucose revealed a deficiency in mounting SOCS-3 expression and gallic acid upregulates this feedback regulatory signal. Gallic acid attenuates DNA damage, maintains glutathione turnover, and suppresses hyperglycemia-induced activation of proinflammatory and prooxidant gene expression. Gallic acid beneficially modulate transcription of functionally diverse groups of genes and its regulation of SOCS-3 and TXNIP signals is a newly identified mechanism that has therapeutic implications.
authors.affiliation: Madras Diabetes Research Foundation & Dr. Mohans' Diabetes Specialities Centre, Gopalapuram, Chennai 600 086, India.
authors.forename: Gokulakrishnan
authors.initials: G
authors.lastname: Kuppan
authors.forename: Jayashree
authors.initials: J
authors.lastname: Balasubramanyam
authors.forename: Finny
authors.initials: F
authors.lastname: Monickaraj
authors.forename: Gayatri
authors.initials: G
authors.lastname: Srinivasan
authors.forename: Viswanathan
authors.initials: V
authors.lastname: Mohan
authors.forename: Muthuswamy
authors.initials: M
authors.lastname: Balasubramanyam
mesh_terms: D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D005707:Gallic Acid / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D009249:NADP / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; D015850:Interleukin-6; C106644:SOCS3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014409:Tumor Necrosis Factor-alpha; D009249:NADP; D005707:Gallic Acid; D005978:Glutathione; D005947:Glucose