Involvement of the nuclear factor-κB pathway in the pathogenesis of endometriosis

González-Ramos, Reinaldo; Langendonckt, Anne Van; Defrère, Sylvie; Lousse, Jean-Christophe; Colette, Sébastien; Devoto, Luigi; Donnez, Jacques

doi:10.1016/j.fertnstert.2010.01.013

Cited by 144 publications

(113 citation statements)

References 169 publications

(215 reference statements)

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“…The canonical pathway of NF-κB is activated in endometriotic lesions, and modulation of NF-κB activity and the consequent cell responses, including proliferation, inflammation and adhesion are important in the development of endometriosis (3,13,24,25). Thus, it is noteworthy that the present study demonstrated that HEABG significantly inhibits the TNF-α-induced activation of NF-κB and AP-1 in HESCs.…”

Section: Discussionsupporting

confidence: 50%

“…TNF-α, a pleiotropic pro-inflammatory cytokine, is regarded as an important regulatory molecule in eliciting inflammatory immune responses in endometriosis, and its abnormal production may contribute to the pathophysiology of endometriosis, including cell proliferation and adhesion (1,12). The nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) transcription factors play key roles in immune and inflammatory responses, and modulate cell proliferation, apoptosis, adhesion, invasion and angiogenesis in several cell types, including endometrial cells (13,14). The activation of NF-κB has been implicated in the early development of endometriotic lesions in vivo (13).…”

Section: Introductionmentioning

confidence: 99%

“…The nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) transcription factors play key roles in immune and inflammatory responses, and modulate cell proliferation, apoptosis, adhesion, invasion and angiogenesis in several cell types, including endometrial cells (13,14). The activation of NF-κB has been implicated in the early development of endometriotic lesions in vivo (13). In particular, AP-1 and NF-κB are the principal transcription factors that regulate the expression of adhesion molecules, such as ICAM-1 and VCAM-1 (15).…”

Section: Introductionmentioning

confidence: 99%

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Hexane extract of aged black garlic reduces cell proliferation and attenuates the expression of ICAM-1 and VCAM-1 in TNF-α-activated human endometrial stromal cells

Kim

Park

Choi

et al. 2013

International Journal of Molecular Medicine

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Abstract. Increasing evidence indicates the potentially crucial roles of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in the pathological process underlying endometriosis. The present study aimed to investigate the effects of a hexane extract of aged black garlic (HEABG) on the proliferation and expression of ICAM-1 and VCAM-1 in tumor necrosis factor-α (TNF-α)-activated human endometrial stromal cells (HESCs) isolated from patients with endometriosis. HESCs were isolated from endometriotic tissues obtained from women with advanced endometriosis who underwent laparoscopic surgery for ovarian endometrioma (n=18). Cell proliferation and cell cycle analysis were assessed by WST-1 assay and flow cytometry, respectively. The expression of ICAM-1 and VCAM-1 was measured by flow cytometry, immunofluorescence staining, immunoblotting and quantitative reverse transcriptase-PCR. The secretion of interleukin-6 (IL-6) was determined by enzyme-linked immunosorbent assay (ELISA). The activation of nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) was detected by electrophoretic mobility shift assay (EMSA) and the activation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and p38 MAPK was analyzed by immunoblotting. Cell proliferation and cell cycle progression were significantly suppressed by HEABG in the TNF-α-induced HESCs through the inhibition of the ERK and JNK signaling pathways. Remarkably, the treatment of the HESCs with HEABG potently suppressed the TNF-α-induced ICAM-1 and VCAM-1 transcript and protein expression by inhibiting the activation of NF-κB and AP-1 transcription factors. Our results suggest that HEABG may be effective in the prevention and treatment of endometriosis in humans.

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Section: Discussionsupporting

confidence: 50%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hexane extract of aged black garlic reduces cell proliferation and attenuates the expression of ICAM-1 and VCAM-1 in TNF-α-activated human endometrial stromal cells

Kim

Park

Choi

et al. 2013

International Journal of Molecular Medicine

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“…TAM signaling also promotes angiogenesis by production of epidermal growth factor, TGF-β and chemokines and stimulates proliferation of NF-KB, migration inhibitory factor (MIF), and IL-1 (Wei et al, 2011). TAM is also associated with extracellular tissue remodeling activity through expression and release of matrix metallopeptidases (MMP) 2 and 9 and urokinase plasminogen activator (UPA) (Yeh et al, 2013 (González-Ramos et al, 2010). These cell processes are involved in the development of endometriosis and ovarian cancer (González-Ramos et al, 2010).…”

Section: Inflammationmentioning

confidence: 99%

Endometriosis, Leiomyoma and Adenomyosis: the Risk of Gynecologic Malignancy

Verit

Yücel²

2013

Asian Pacific Journal of Cancer Prevention

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“…2) (Gonzalez-Ramos et al). NF-κB mediated gene transcription promoting inflammation, invasion, angiogenesis, and cell proliferation and inhibiting apoptosis of endometriotic cells through p50/p65 dimers and NF-κB inhibitor IκB has been found in vitro and in vivo studies (Gonzalez-Ramos et al, 2010). Constitutive activation of NF-κB has been demonstrated in endometriotic lesions and peritoneal macrophages of patients with endometriosis (Laird et al, 2000).…”

Section: Molecular Modulationsmentioning

confidence: 98%