+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Tumor necrosis factor-alpha-induced interleukin-8 (IL-8) expression in endometriotic stromal cells, probably through nuclear factor-kappa B activation: gonadotropin-releasing hormone agonist treatment reduced IL-8 expression



Tumor necrosis factor-alpha-induced interleukin-8 (IL-8) expression in endometriotic stromal cells, probably through nuclear factor-kappa B activation: gonadotropin-releasing hormone agonist treatment reduced IL-8 expression



Journal of Clinical Endocrinology and Metabolism 88(2): 730-735



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.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 047850073

Download citation: RISBibTeXText

PMID: 12574206

DOI: 10.1210/jc.2002-020666


Related references

Thalidomide inhibits tumor necrosis factor-alpha-induced interleukin-8 expression in endometriotic stromal cells, possibly through suppression of nuclear factor-kappaB activation. Journal of Clinical Endocrinology and Metabolism 90(5): 3017-3021, 2005

Progesterone and progestational compounds attenuate tumor necrosis factor alpha-induced interleukin-8 production via nuclear factor kappa B inactivation in endometriotic stromal cells. Fertility and Sterility 83(5): 1530-1535, 2005

Insulin-like growth factor-1 downregulates nuclear factor kappa B activation and upregulates interleukin-8 gene expression induced by tumor necrosis factor alpha. Biochemical and Biophysical Research Communications 305(4): 831-839, 2003

Interleukin-1 beta and tumor necrosis factor-alpha induce expression of alpha 1-antichymotrypsin in human astrocytoma cells by activation of nuclear factor-kappa B. Journal of Neurochemistry 67(5): 2039-2044, 1996

Tumor necrosis factor-alpha induced the release of interleukin-6 from endometriotic stromal cells by the nuclear factor-kappaB and mitogen-activated protein kinase pathways. Fertility and Sterility 82(Suppl. 3): 1023-1028, 2004

Nuclear factor-kappa B is required for tumor necrosis factor-alpha-induced manganese superoxide dismutase expression in human endometrial stromal cells. Journal of Clinical Endocrinology and Metabolism 87(8): 3845-3850, 2002

Lipopolysaccharide-promoted proliferation of endometriotic stromal cells via induction of tumor necrosis factor alpha and interleukin-8 expression. Fertility and Sterility 82(Suppl. 3): 1036-1042, 2004

Pycnogenol inhibits tumor necrosis factor-alpha-induced nuclear factor kappa B activation and adhesion molecule expression in human vascular endothelial cells. Cellular and Molecular Life Sciences 57(5): 834-841, 2000

Activation of the nuclear factor kappa B is not sufficient for regulation of tumor necrosis factor-induced interleukin-6 gene expression. Biochimie 75(11): 1007-1018, 1993

Tumor necrosis factor-alpha promotes proliferation of endometriotic stromal cells by inducing interleukin-8 gene and protein expression. Journal of Clinical Endocrinology and Metabolism 85(2): 824-829, 2000

Regulation of interleukin-2 receptor alpha chain expression and nuclear factor.kappa B activation by protein kinase C in T lymphocytes. Autocrine role of tumor necrosis factor alpha. Journal of Biological Chemistry 269(39): 24424, 1994

Peroxisome proliferator-activated receptor-gamma ligand reduced tumor necrosis factor-alpha-induced interleukin-8 production and growth in endometriotic stromal cells. Fertility and Sterility 89(2): 311-317, 2008

Reduced expression of adipose triglyceride lipase enhances tumor necrosis factor alpha-induced intercellular adhesion molecule-1 expression in human aortic endothelial cells via protein kinase C-dependent activation of nuclear factor-kappaB. Journal of Biological Chemistry 286(37): 32045-32053, 2011

17 beta-estradiol inhibits tumor necrosis factor-alpha-induced nuclear factor-kappa B activation by increasing nuclear factor-kappa B p105 level in MCF-7 breast cancer cells. Biochemical and Biophysical Research Communications 279(1): 47-52, 2000

Guanine-nucleotide exchange factor H1 mediates lipopolysaccharide-induced interleukin 6 and tumor necrosis factor α expression in endothelial cells via activation of nuclear factor κB. Shock 37(5): 531-538, 2012