Estriol Inhibits Dermcidin Isoform-2 Induced Inflammatory Cytokine Expression Via Nitric Oxide Synthesis in Human Neutrophil
13 Mar 2019-Current Molecular Medicine (Bentham Science Publishers Ltd.)-Vol. 18, Iss: 10, pp 672-678
TL;DR: The stress-induced dermcidin isoform-2 (DCN-2) production in AIHD propagates the inflammatory response and Steroid molecule like estriol plays a protective role by reducing DCn-2 responses in the NO synthesis.
Abstract: Background An increase in the level of cytokines like TNF-α and IL-6 causes the inflammatory surge in acute ischemic heart disease (AIHD). Objective A high-level dermcidin isoform-2 (DCN-2) occurrence in AIHD was subjected to determine a possible regulation of cytokines expression. The effect of estrogen to counteract the inflammatory response was determined. Methods Blood was collected from AIHD patients and normal volunteers with consent. Nitric oxide (NO) synthesis was done with methemoglobin method.TNF-α and IL-6 expression were determined by ELISA and Western blot. Results (DCN-2) incubation with 120nM to the normal neutrophil solution for 2h resulted in the increase of TNF-α from 3.82±1.53pg/ml to 20.7±6.9pg/ml and IL-6 from 3.27±1.52pg/ml to 47.07±3.4pg/ml. In AIHD patients, the cytokine level was18.3- 27.3pg/ml, with a median value 21.86pg/ml (TNF-α) and IL-6 level was 23.54- 52.73pg/ml, with a median value 42.16pg/ml. Treatment with 0.6nM estriol, a kind of female steroid hormone estrogen for 45min decreased the elevated cytokine level in 120nM DCN-2 treated normal neutrophils. DCN-2 induced TNF-α synthesis in neutrophils was further determined by Western blot technique with a thickened band intensity of TNF-α. Estriol (0.6nM) treatment also influenced the DCN-2 induced inhibition of nitric oxide (NO) synthesis from 0nmol NO/ml to 0.56nmol/ml. The subsequent reduction of TNF-α level correlates the increase of NO level. Conclusion In conclusion, the stress-induced DCN-2 production in AIHD propagates the inflammatory response. Steroid molecule like estriol plays a protective role by reducing DCN-2 responses in the NO synthesis.
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...Estriol, one kind of estrogen shows anti– inflammatory([135]) and anti-coagulator effect....
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TL;DR: Explorations of this work may uncover the role of sulfation metabolism of any biomolecule on cellular glycemic regulation and possible association of some SULT-isoform with hepatic fat-regulations may indicate an unfocused link between calorie-metabolism and the glycemic-state of the individuals.
Abstract: Aims To study the effects of blood glucose regulating compounds on human and rat sulfotransferases (SULTs) expressions. Background Phase-II enzymes, sulfotransferases catalyze the sulfuryl-group-transfer to endogenous/exogenous compounds. The alteration of expressions of SULTs may have influence on the sulfation rate of their corresponding substrates. Objectives The influence of the altered biotransformation property might impair or adjust several biochemical events, drug-drug interactions or modifications of bioaccumulation or excretion pattern of certain drug. Methods In this brief study, diabetes inducing drug streptozotocin (STZ 10 or 50 mg/kg to male Sprague Dawley rat for 2 weeks) or hyperglycemia controlling drug tolbutamide (TLB 0.1 or 10µM to human hepato-carcinoma cells, HepG2 for 10 days) was applied and the SULTs expressions were verified. Extensive protein-protein (STa, SULT2A1/DHEAST) interactions were studied by the STRING (Search-Tool-for-the-Retrieval-of-Interacting Genes/Proteins) Bioinformaticssoftware. Results Present result suggests that while STZ increased the STa (in rat) (dehydroepiandrosterone catalyzing SULT; DHEAST in human HepG2), tolbutamide decreased PPST (phenol catalyzing SULT) and DHEAST activity in human Hep G2 cells. Moderate decrease in MPST (monoamine catalyzing SULT) and EST (estrogen catalyzing) activity is noticed in this case also. STa/DHEAST was found to be highly interactive to SHBG/sex-hormone-binding-globulin; PPARα/lipidmetabolism-regulator; FABP1/fatty-acid-binding-protein. Conclusions In brief, streptozotocin and tolbutamide, two glycaemia-modifying drugs demonstrate rat and human SULTs regulating activities. The reciprocal nature of these two drugs on SULTs expression may be associated with their contrasting abilities in glucose-homeostasis. Possible association of some SULT-isoform with hepatic fat-regulations may indicate an unfocused link between calorie-metabolism and the glycemic-state of the individuals. Explorations of this work may uncover the role of sulfation metabolism of any biomolecule on cellular glycemic regulation.