Tumor Necrosis Factor-α-Induced Interleukin-8 (IL-8) Expression in Endometriotic Stromal Cells, Probably through Nuclear Factor-κB Activation: Gonadotropin-Releasing Hormone Agonist Treatment Reduced IL-8 Expression
| Autor: | Sayako Horie, Tasuku Harada, Yasuko Sakamoto, Tomio Iwabe, Souichi Yoshida, Yumiko Iba, Fuminori Taniguchi, Naoki Terakawa |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Adult
Agonist medicine.medical_specialty Stromal cell medicine.drug_class Endocrinology Diabetes and Metabolism Clinical Biochemistry Endometriosis Uterus Gene Expression Antineoplastic Agents Electrophoretic Mobility Shift Assay Biology Biochemistry Gonadotropin-Releasing Hormone Endocrinology NF-KappaB Inhibitor alpha Western blot Gonadotropin-releasing hormone agonist Internal medicine Gene expression medicine Humans RNA Messenger Interleukin 8 Phosphorylation Cells Cultured Protein Synthesis Inhibitors medicine.diagnostic_test Tumor Necrosis Factor-alpha Tosylphenylalanyl Chloromethyl Ketone Interleukin-8 Biochemistry (medical) NF-kappa B Estrogens medicine.anatomical_structure Female I-kappa B Proteins Tumor necrosis factor alpha Stromal Cells |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 88:730-735 |
| ISSN: | 1945-7197 0021-972X |
| DOI: | 10.1210/jc.2002-020666 |
| Popis: | Endometriosis, a common disease among women of reproductive age, is characterized by the presence of endometrial-like tissue outside the uterus. We previously reported that TNFalpha promoted proliferation of endometriotic stromal cells by inducing IL-8 gene and protein expression. We hypothesize that TNFalpha may induce IL-8 production in endometriotic cells through nuclear factor-kappa B (NF-kappa B) activation. Western blot analyses and electrophoretic mobility shift assays revealed that incubation with TNF alpha induced the expression of phosphorylated inhibitor kappa B (p-I kappa B) and activation of NF-kappa B in endometriotic stromal cells. The NF-kappa B inhibitor, N-tosyl-L-phenylalanine chloromethyl ketone, reduced TNFalpha-induced IL-8 gene and protein expression. The medical treatment of endometriosis with GnRH agonist (GnRHa) has been shown to induce hypoestrogenemia and reduce the observable number of endometriotic implants. We compare the expression of IL-8 gene and protein in endometriotic stromal cells of patients treated with GnRHa and those of patients without treatment before laparoscopic cystectomy for endometrioma. The addition of TNFalpha (0.1 ng/ml) significantly increased protein and gene expression of IL-8 in the cells of patients without GnRHa treatment, but this expression was not observed in the cells of patients with GnRHa. The addition of estradiol (E2; 10(-7) M) enhanced the expression of IL-8. However, in the cells of patients who received GnRHa treatment, TNFalpha and E2 did not show any significant effect. In endometriotic stromal cells without GnRHa treatment, TNFalpha and E2 increased the expression of p-I kappa B. In contrast, TNFalpha and E2 had no significant effect on the expression of p-I kappa B in cells that received GnRHa treatment. These findings demonstrate that NF-kappa B activation is critical for TNFalpha-induced IL-8 expression in endometriotic stromal cells. The current study showed for the first time that GnRHa treatment attenuated the expression of IL-8 by reducing TNFalpha-induced NF-kappa B activation. |
| Databáze: | OpenAIRE |
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