17beta-Estradiol Inhibits MCP-1 Production in Human Keratinocytes

Kanda, Naoko; Watanabe, Shinichi

doi:10.1046/j.1523-1747.2003.12255.x

Cited by 44 publications

(55 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ketoconazole is an antifungal drug with therapeutic efficacy in prostate cancer and other benign and malignant neoplastic conditions (e.g., cutaneous papillomatosis) (Yamamoto et al, 2000;Hamaguchi et al, 2002;Tzanakakis et al, 2002;Kanda and Watanabe, 2002b;Berthold et al, 2005). Ketoconazole inhibits cytochrome P450-dependent enzyme 11-hydroxylase activity, which suppresses testosterone production leading to inhibition of testosterone-dependent prostate cancer cell growth (Loose et al, 1983).…”

Section: Discussionmentioning

confidence: 99%

“…Ketoconazole inhibits cytochrome P450-dependent enzyme 11-hydroxylase activity, which suppresses testosterone production leading to inhibition of testosterone-dependent prostate cancer cell growth (Loose et al, 1983). Its pleiotropic inhibitory activity is evident from the fact that several P450-and non-P450-dependent enzymes (e.g., CYP3A4, UGT, aryl-hydrocarbon hydroxylase and 7-ethoxyresorufin-deethylase) are inhibited, as are other enzymes such as adenylate cyclase, 5-lipoxygenase or calmodulindependent enzymes (Beetens et al, 1986;Stalla et al, 1988;Dresser et al, 2000;Venkatakrishnan et al, 2000;Kanda and Watanabe, 2002b;Yong et al, 2005). However, ketoconazole is less well established as a transcriptional regulator of genes involved in drug or cholesterol metabolism and cyclic adenosine 3 0 ,5 0 monophosphate signaling (Takagi et al, 1989;Kim, 1992;Ellsworth et al, 1994;Kanda and Watanabe, 2002a, b).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Inhibition of drug metabolism by blocking the activation of nuclear receptors by ketoconazole

et al. 2006

View full text Add to dashboard Cite

Individual variation in drug metabolism is a major cause of unpredictable side effects during therapy. Drug metabolism is controlled by a class of orphan nuclear receptors (NRs), which regulate expression of genes such as CYP (cytochrome)3A4 and MDR-1 (multi-drug resistance-1), that are involved in this process. We have found that xenobiotic-mediated induction of CYP3A4 and MDR-1 gene transcription was inhibited by ketoconazole, a commonly used antifungal drug. Ketoconazole mediated its effect by inhibiting the activation of NRs, human pregnenolone X receptor and constitutive androstene receptor, involved in regulation of CYP3A4 and MDR-1. The effect of ketoconazole was specific to the group of NRs that control xenobiotic metabolism. Ketoconazole disrupted the interaction of the xenobiotic receptor PXR with the co-activator steroid receptor co-activator-1. Ketoconazole treatment resulted in delayed metabolism of tribromoethanol anesthetic in mice, which was correlated to the inhibition of PXR activation and downmodulation of cyp3a11 and mdr-1 genes and proteins. These studies demonstrate for the first time that ketoconazole represses the coordinated activation of genes involved in drug metabolism, by blocking activation of a specific subset of NRs. Our results suggest that ketoconazole can be used as a pan-antagonist of NRs involved in xenobiotic metabolism in vivo, which may lead to novel strategies that improve drug effect and tolerance.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Inhibition of drug metabolism by blocking the activation of nuclear receptors by ketoconazole

et al. 2006

View full text Add to dashboard Cite

show abstract

“…35,59 The human MCP-1 promoter has accordingly been shown to be activated by several transcription factors including NFjB, Sp1 or AP-1. 37,[60][61][62] Also emphasizing the importance of the cellular context, we observed that the transfection of TCF-4 alone led to an upregulation of the MCP-1 promoter activity in the BT549 and Hs578T cells in which b-catenin is abundantly found in the nucleus. 34 This endogenous level of nuclear b-catenin might thus be sufficient to activate the MCP-1 promoter in the presence of TCF-4.…”

Section: Discussionmentioning

confidence: 99%

Transactivation of MCP‐1/CCL2 by β‐catenin/TCF‐4 in human breast cancer cells

Mestdagt

Polette

Butticè

et al. 2005

Intl Journal of Cancer

View full text Add to dashboard Cite

The loss of E-cadherin expression and the translocation of b-catenin to the nucleus are frequently associated with the metastatic conversion of epithelial cells. In the nucleus, b-catenin binds to the TCF/LEF-1 (T-cell factor/ lymphoid enhancer factor) transcription factor family resulting in the activation of several genes, some of them having important implications in tumour progression. In our study, we investigated the potential regulation of monocyte chemotactic protein-1 (MCP-1/CCL2) expression by the b-catenin/TCF pathway. This CC-chemokine has been implicated in tumour progression events such as angiogenesis or tumour associated macrophage (TAM) infiltration. We thus demonstrated that MCP-1 expression correlates with the reorganization of the E-cadherin/b-catenin complexes. Indeed, MCP-1 was expressed by invasive breast cancer cells (MDA-MB-231, BT549 and Hs578T), which do not express E-cadherin but was not produced by noninvasive breast cancer cell lines (MCF7 and T47D) expressing high level of E-cadherin. In addition, the MCP-1 promoter was activated in BT549 breast cancer cells transfected with b-catenin and TCF-4 cDNAs. The MCP-1 mRNA level was similarly upregulated. Moreover, we showed that MCP-1 mRNA was downregulated after transfection with a siRNA against b-catenin in both BT549 and Hs578T cells. Our results therefore identify MCP-1 as a target of the b-catenin/TCF/LEF pathway in breast tumour cells, a regulation which could play a key role in breast tumour progression. ' 2005 Wiley-Liss, Inc.Key words: MCP-1; b-catenin; breast cancer Chemokines constitute a superfamily of proinflammatory cytokines that are implicated in tumour progression, modulating not only host tumour-specific immunological response but also angiogenesis or tumour cell invasion and proliferation. 1-3 Monocyte chemotactic protein-1 (MCP-1) or CCL2 is a CC-chemokine that specifically attracts monocytes and memory T cells. It has been particularly implicated in processes characterized by mononuclear cell infiltration including breast cancer. 4,5 In some models, MCP-1 has been shown to display an antitumoral effect. 6,7 Nevertheless, a large number of studies demonstrate that MCP-1 facilitates tumour progression through its ability to recruit stromal cells including tumour associated macrophages (TAMs) and endothelial cells. 7-10 A pro-angiogenic role of MCP-1 has been demonstrated in many systems, facilitating tumour growth and dissemination. 8,9,11,12 Moreover, a direct effect of MCP-1 on tumour cell migration in vitro has also been described. 13 Recently, Lebrecht et al. 14 have correlated an increased MCP-1 serum level with an advanced breast tumour stage and the presence of lymph node metastasis. In the same way, Amann et al. 15 reported a significant association between MCP-1 urinary levels and tumour stage and grade. They suggested a use of its urinary level as prognosis marker in bladder cancer. The correlation between MCP-1 expression and a poor prognosis was also demonstrated for the squamous cell carcinoma of the oeso...

show abstract

“…33 Estradiol also regulates innate immunity by suppressing the secretion and/or expression of proinflammatory mediators by epithelial cells. For example, in human keratinocytes, Kande and Watanabe [34][35][36] demonstrated the suppression of MCP-1, regulated upon activation, normal T-cell expressed and secreted (RANTES), and IP-10 with E 2 treatment. Estradiol was also shown to suppress TLR3-induced IL-6, IL-8, and IP-10 secretion from human virally transfected endometrial cell lines.…”

Section: Introductionmentioning

confidence: 99%

Estradiol selectively regulates innate immune function by polarized human uterine epithelial cells in culture

et al. 2008

View full text Add to dashboard Cite

The goal of this study was to examine the role of E 2 in regulating innate immune protection by human uterine epithelial cells (UECs). Recognizing that UECs produce cytokines and chemokines to recruit and activate immune cells as well as viral and bacterial antimicrobials, we sought to examine the effect of E 2 on constitutive and Toll-like receptor (TLR) agonist (lipopolysaccharide (LPS) and poly (I:C))-induced immune responses. The secretion by polarized UECs in culture of interleukin (IL)-6, macrophage inhibitory factor (MIF), and secretory leukocyte protease inhibitor (SLPI) was examined as well as the mRNA expression of human β-defensin-2 (HBD2), tumor necrosis factor (TNF)-α, IL-8, and nuclear factor (NF)-kB. When incubated with E 2 for 24-48 h, we found that E 2 stimulated UEC secretion of SLPI (fourfold) and mRNA expression of HBD2 (fivefold). Moreover, when antibacterial activity in UEC secretions was measured using Staphylococcus aureus, E 2 increased the secretion of soluble factor(s) with antibacterial activity. In contrast, E 2 had no effect on constitutive secretion of proinflammatory cytokines and chemokines by UECs but completely inhibited LPS-and poly (I:C)-induced secretion of MIF, IL-6, and IL-8. Estradiol also reversed the stimulatory effects of IL-1β on mRNA expression of TNF-α, IL-8, and NF-kB by 85, 95, and 70%, respectively. As SLPI is known to inhibit NF-kB expression, these findings suggest that E 2 inhibition of proinflammatory cytokines may be mediated through SLPI regulation of NF-kB. Overall, these findings indicate that the production of cytokines, chemokines, and antimicrobials by UECs are differentially regulated by E 2 . Further, it suggests that with E 2 regulation, epithelial cells that line the uterine cavity have evolved immunologically to be sensitive to viral and bacterial infections as well as the constraints of procreation.

show abstract

17beta-Estradiol Inhibits MCP-1 Production in Human Keratinocytes

Cited by 44 publications

References 57 publications

Inhibition of drug metabolism by blocking the activation of nuclear receptors by ketoconazole

Inhibition of drug metabolism by blocking the activation of nuclear receptors by ketoconazole

Transactivation of MCP‐1/CCL2 by β‐catenin/TCF‐4 in human breast cancer cells

Estradiol selectively regulates innate immune function by polarized human uterine epithelial cells in culture

Contact Info

Product

Resources

About