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Accumulating evidence indicates that epigenetic aberrations have a role in the pathogenesis of rheumatoid arthritis (RA). However, reports on histone modifications are as yet quite limited in RA. Interleukin (IL)-6 is an inflammatory cytokine which is known to be involved in the pathogenesis of RA. Here we report the role of histone modifications in elevated IL-6 production in RA synovial fibroblasts (SFs). The level of histone H3 acetylation (H3ac) in the IL-6 promoter was significantly higher in RASFs than osteoarthritis (OA) SFs. This suggests that chromatin structure is in an open or loose state in the IL-6 promoter in RASFs. Furthermore, curcumin, a histone acetyltransferase (HAT) inhibitor, significantly reduced the level of H3ac in the IL-6 promoter, as well as IL-6 mRNA expression and IL-6 protein secretion by RASFs. Taken together, it is suggested that hyperacetylation of histone H3 in the IL-6 promoter induces the increase in IL-6 production by RASFs and thereby participates in the pathogenesis of RA., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Fructooligosaccharides (FOS) are indigestible oligosaccharides that increase calcium absorption by the colorectum in rats, but the underlying mechanisms remain unclear. We therefore investigated the effects of FOS on expressions of genes involved with calcium absorption in rat colorectal mucosa cells. After feeding a diet containing FOS (100 g/kg diet) to rats for 2 d, we investigated gene transcripts of transient receptor potential vanilloid type 6 (TRPV6), calbindin-D9k, and plasma membrane calcium-ATPase 1b (PMCA1b). The FOS diet increased expression of TRPV6 and calbindin-D9k but did not affect PMCA1b expression. Because FOS could not directly affect gene expression, SCFA formed as fermentation products of FOS were considered as likely intermediates. SCFA (2.0 mmol/L) were thus added to Caco-2 human colonic epithelial cells, resulting in significantly increased mRNA expression of TRPV6. To ascertain the effects of SCFA on mRNA expression, a genomic clone of TRPV6 was isolated. Using luciferase reporter assay, a segment between -71 nucleotides and the translation start site was found to contain a positive responsive element to SCFA. These results suggest that FOS increase calcium absorption by increasing mRNA expression of TRPV6 in rat colorectum, and cell culture analysis indicated that SCFA, as fermentation products of FOS, are involved in the increased mRNA expression of TRPV6. We found for the first time, to our knowledge, that regulation of TRPV6 gene expression by SCFA may be a molecular mechanism involved in the promotion of calcium absorption by FOS in rats.

Berberine is an isoquinoline alkaloid isolated from Coptidis rhizoma, a major herb widely used in Chinese herbal medicine. Berberine's biological activity includes antidiarrheal, antimicrobial, and anti-inflammatory effects. Recent findings show that berberine prevents neuronal damage due to ischemia or oxidative stress and that it might act as a novel cholesterol-lowering compound. The accumulation of amyloid-beta peptide (Abeta) derived from amyloid precursor protein (APP) is a triggering event leading to the pathological cascade of Alzheimer's disease (AD); therefore the inhibition of Abeta production should be a rational therapeutic strategy in the prevention and treatment of AD. Here, we report that berberine reduces Abeta levels by modulating APP processing in human neuroglioma H4 cells stably expressing Swedish-type of APP at the range of berberine concentration without cellular toxicity. Our results indicate that berberine would be a promising candidate for the treatment of AD.