Glucocorticoid-Induced Reversal of Interleukin-1β-Stimulated Inflammatory Gene Expression in Human Oviductal Cells
نویسندگان
چکیده
Studies indicate that high-grade serous ovarian carcinoma (HGSOC), the most common epithelial ovarian carcinoma histotype, originates from the fallopian tube epithelium (FTE). Risk factors for this cancer include reproductive parameters associated with lifetime ovulatory events. Ovulation is an acute inflammatory process during which the FTE is exposed to follicular fluid containing both pro- and anti-inflammatory molecules, such as interleukin-1 (IL1), tumor necrosis factor (TNF), and cortisol. Repeated exposure to inflammatory cytokines may contribute to transforming events in the FTE, with glucocorticoids exerting a protective effect. The global response of FTE cells to inflammatory cytokines or glucocorticoids has not been investigated. To examine the response of FTE cells and the ability of glucocorticoids to oppose this response, an immortalized human FTE cell line, OE-E6/E7, was treated with IL1β, dexamethasone (DEX), IL1β and DEX, or vehicle and genome-wide gene expression profiling was performed. IL1β altered the expression of 47 genes of which 17 were reversed by DEX. DEX treatment alone altered the expression of 590 genes, whereas combined DEX and IL1β treatment altered the expression of 784 genes. Network and pathway enrichment analysis indicated that many genes altered by DEX are involved in cytokine, chemokine, and cell cycle signaling, including NFκΒ target genes and interacting proteins. Quantitative real time RT-PCR studies validated the gene array data for IL8, IL23A, PI3 and TACC2 in OE-E6/E7 cells. Consistent with the array data, Western blot analysis showed increased levels of PTGS2 protein induced by IL1β that was blocked by DEX. A parallel experiment using primary cultured human FTE cells indicated similar effects on PTGS2, IL8, IL23A, PI3 and TACC2 transcripts. These findings support the hypothesis that pro-inflammatory signaling is induced in FTE cells by inflammatory mediators and raises the possibility that dysregulation of glucocorticoid signaling could contribute to increased risk for HGSOC.
منابع مشابه
Immunomodulatory Effects of Bee Venom in Human Synovial Fibroblast Cell Line
As in Iranian traditional medicine, bee venom (BV) is a promising treatment for the rheumatoid arthritis (RA) which is considered as a problematic human chronic inflammatory disease in the present time. Smoking is considered to be a major risk factor in RA onset and severity. The main aim of this study is to investigate the effects of BV on cigarette smoke-induced inflammatory response in fibro...
متن کاملImmunomodulatory Effects of Bee Venom in Human Synovial Fibroblast Cell Line
As in Iranian traditional medicine, bee venom (BV) is a promising treatment for the rheumatoid arthritis (RA) which is considered as a problematic human chronic inflammatory disease in the present time. Smoking is considered to be a major risk factor in RA onset and severity. The main aim of this study is to investigate the effects of BV on cigarette smoke-induced inflammatory response in fibro...
متن کاملReduction of NADH oxidase, NO synthase, TNFα, and IL-1β mRNA expression levels on lipopolysacharide-stimulated murine macrophages by Zataria Multiflora
Zataria multiflora (ZM) is a thyme-like aromatic plant in the Lamiaceae family that grows in central and southern Iran. ZM is extensively used as a flavor ingredient in a wide variety of foods and is used as part of popular traditional folk remedies. In the present study, ZM essential oil (ZMO) was obtained from ZM leaves via hydro-distillation and then analyzed by GC-MS (gas chromatography-mas...
متن کاملRole of Propolis as a pharmaceutical candidate on interleukin-1β proinflammatory cytokine expression in Alzheimer's rat
Background: One of the important factors that play a key role in the pathogenesis of Alzheimer's disease (AD) is inflammatory processes leading to impaired expression of inflammatory cytokines such as interleukin-6, TNF-α, and interleukin-1β (IL-1β). Propolis, as a therapeutic compound, has anti-inflammatory and antioxidant properties. Therefore, the aim of the present study was to investigate ...
متن کاملBio-functions of carvacrol-supplemented feeds on lipopolysaccharide-induced rainbow trout (Oncorhynchus mykiss Walbaum, 1792)
To investigate the effects of carvacrol supplementation diets in rainbow trout induced by LPS, we measured gene expressions relative to pro-inflammatory and apoptosis in kidney and liver. Fish, which that were studied by four different treatments with three replicates each, was 44.71±1.33 gr. All fish were infected with E. coli LPS (25 µg ml-1) expect control and only carvacrol containing diet ...
متن کامل