Thalidomide Inhibits Tumor Necrosis Factor-α-Induced Interleukin-8 Expression in Endometriotic Stromal Cells, Possibly through Suppression of Nuclear Factor-κB Activation
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Thalidomide treatment attenuated tumor necrosis factor-alpha-induced interleukin-8 expression and nuclear factor-kappaB activation in human endometriotic stromal cells.
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Abstract
OBJECTIVE: Endometriosis, a common disease among women of reproductive age, is characterized by the presence of endometrial-like tissue outside the uterus. TNF-alpha induces IL-8 production in endometriotic cells through nuclear factor-kappaB (NF-kappaB) activation. Thalidomide (Thal) inhibits inflammation by down-regulating the expression of proinflammatory cytokines in tumor cells and inflammatory cells. However, the mechanism of Thal action in human endometriotic stromal cells has not yet been elucidated. MAIN OUTCOME MEASURES: We examined whether Thal abrogates TNF-alpha-induced up-regulation of IL-8 expression in endometriotic stromal cells. RESULTS: Here, we show 1) that treatment of endometriotic stromal cells with TNF-alpha increased the expression of phosphorylated IkappaBalpha and degradation of total IkappaBalpha, which in turn activates NF-kappaB; 2) Thal significantly inhibits the TNF-alpha-induced expression of phosphorylated IkappaBalpha and degradation of IkappaBalpha; 3) TNF-alpha activation induced increased nuclear translocation of NF-kappaB, which was inhibited by pretreatment with either Thal or N-tosyl-L-phenylalanine chloromethyl ketone, an NF-kappaB inhibitor. Thal did not enhance the N-tosyl-L-phenylalanine chloromethyl ketone's action; and 4) Pretreatment with Thal reduced TNF-alpha-induced IL-8 protein production as well as mRNA expression. CONCLUSION: The current study showed for the first time that Thal treatment attenuated the expression of IL-8 by reducing TNF-alpha-induced NF-kappaB activation.
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- Thalidomide Reduces Cell Proliferation in Endometriosis Experimentally Induced in Rats 2019
- Endometriotic cell culture contamination and authenticity: a source of bias in <i>in vitro</i> research? 2019
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- Non‐hormonal targets underlying endometriosis: A focus on molecular mechanisms 2015
- Thalidomide affects experimental endometriosis: A randomized controlled study in the rat 2014
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- Curcumin Attenuates TNF‐α‐induced Expression of Intercellular Adhesion Molecule‐1, Vascular Cell Adhesion Molecule‐1 and Proinflammatory Cytokines in Human Endometriotic Stromal Cells 2011
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- Involvement of iron, nuclear factor-kappa B (NF-KB) and prostaglandins in the pathogenesis of peritoneal endometriosis-associated inflammation: A review 2009
- NF-κB Decoy Oligonucleotides Suppress RANTES Expression and Monocyte Chemotactic Activity via NF-κB Inactivation in Stromal Cells of Ectopic Endometrium 2009
- Involvement of Iron, Nuclear Factor-Kappa B (NF-κB) and Prostaglandins in the Pathogenesis of Peritoneal Endometriosis-Associated Inflammation: A Review 2009
- Emerging drugs for endometriosis 2008
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- Agents Blocking the Nuclear Factor-κB Pathway Are Effective Inhibitors of Endometriosis in an in vivo Experimental Model 2007
- Nuclear Factor-κB (NF-κB): An Unsuspected Major Culprit in the Pathogenesis of Endometriosis That Is Still at Large? 2006
- A Novel Noninvasive Model of Endometriosis for Monitoring the Efficacy of Antiangiogenic Therapy 2006
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