Increased activation of nuclear factor-kappa B (NF-κB) in isolated peritoneal macrophages of patients with endometriosis

Lousse, Jean-Christophe; Langendonckt, Anne Van; González-Ramos, Reinaldo; Defrère, Sylvie; Renkin, Emmanuelle; Donnez, Jacques

doi:10.1016/j.fertnstert.2007.06.015

Cited by 84 publications

(83 citation statements)

References 19 publications

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“…The lesions consistently contain infiltrating macrophages, which display clear features of being phagocytic cells, locally activated and not just passively entrapped in the ectopic tissues. 3,30 -37 The depletion of all phagocytic cells 7,38 and the interference with the NF-B transcription factor-dependent pathway, 39 which is activated in macrophages infiltrating endometriotic lesions, 33 attenuate the disease in models of endometriosis, further supporting the direct involvement of activated macrophages in the natural history of the disease.…”

Section: Discussionmentioning

confidence: 99%

Proangiogenic Tie2+ Macrophages Infiltrate Human and Murine Endometriotic Lesions and Dictate Their Growth in a Mouse Model of the Disease

Capobianco

Monno

Cottone

et al. 2011

The American Journal of Pathology

101

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Section: Discussionmentioning

confidence: 99%

Proangiogenic Tie2+ Macrophages Infiltrate Human and Murine Endometriotic Lesions and Dictate Their Growth in a Mouse Model of the Disease

Capobianco

Monno

Cottone

et al. 2011

The American Journal of Pathology

101

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“…1,26 -31 For example, the nuclear factor-B transcription factor is activated in macrophages from endometriotic patients 27 and responsive genes that determine macrophages functions undergo transactivation, supporting angiogenesis and tissue remodeling 32,33 Accordingly, the in vivo inhibition of nuclear factor-B interferes with the growth of experimental lesions. 34 The environmental cues that activate peritoneal macrophages are still uncertain: local hypoxia apparently plays a major role.…”

Section: Discussionmentioning

confidence: 99%

Macrophages Are Alternatively Activated in Patients with Endometriosis and Required for Growth and Vascularization of Lesions in a Mouse Model of Disease

Bacci

Capobianco

Monno

et al. 2009

The American Journal of Pathology

356

348

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The mechanisms that sustain endometrial tissues at ectopic sites in patients with endometriosis are poorly understood. Various leukocytes , including macrophages, infiltrate endometriotic lesions. In this study, we depleted mouse macrophages by means of either clodronate liposomes or monoclonal antibodies before the injection of syngeneic endometrial tissue. In the absence of macrophages, tissue fragments adhered and implanted into the peritoneal wall, but endometriotic lesions failed to organize and develop. When we depleted macrophages after the establishment of endometriotic lesions, blood vessels failed to reach the inner layers of the lesions, which stopped growing. Macrophages from patients with endometriosis and experimental mice, but not nonendometriotic patients who underwent surgery for uterine leiomyomas or control mice , expressed markers of alternative activation. These markers included high levels of scavenger receptors, CD163 and CD206, which are involved in both the scavenging of hemoglobin with iron transfer into macrophages and the silent clearance of inflammatory molecules. Macrophages in both inflammatory liquid and ectopic lesions were equally polarized, suggesting a critical role of environmental cues in the peritoneal cavity.Adoptively transferred, alternatively activated macrophages dramatically enhanced endometriotic lesion growth in mice. Inflammatory macrophages effectively protected mice from endometriosis. Therefore, endogenous macrophages involved in tissue remodeling appear as players in the natural history of endometriosis, required for effective vascularization and ectopic lesion growth.

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“…This is a proinflammatory disease, with an increased peritoneal fluid volume that contains increased concentrations of white blood cells and activated peritoneal macrophages, which together with endometriotic lesions and macroscopically normal peritoneum are significant contributors to IL6 production and also other inflammatory and invasive molecules mediated by local NFKB activation (Hastings & Fazleabas 2006, Kyama et al 2006, Ulukus et al 2006, Lousse et al 2008, Montagna et al 2008. In the present study, IL6 was exclusively analysed in ex vivo eutopic endometrium, making a difference from those reports using ectopic endometrium or stromal cell cultures in which the paracrine communication of cell compartment was lost.…”

Section: Discussionmentioning

confidence: 99%

Nuclear factor κB pathway and interleukin-6 are affected in eutopic endometrium of women with endometriosis

Ponce¹,

Torres²,

Galleguillos³

et al. 2009

Reproduction

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In order to investigate the role of the nuclear factor kB (NFKB) pathway on gene expression in the eutopic endometrium in endometriosis, and in particular of interleukin-6 (IL6), we evaluated RELA, IkB kinase (CHUK), NFKBIA and IL6 expressions and NFKB DNA binding in eutopic endometrium from women with endometriosis. Eutopic endometrium was obtained from 37 women with endometriosis and 42 fertile women during laparoscopy. We analysed RELA, CHUK, NFKBIA and IL6 mRNA levels (RT-PCR); RELA, CHUK and NFKBIA proteins and p-NFKBIA/NFKBIA ratio (western blot); and NFKB binding (DNA shift assay) and IL6 concentration (ELISA) in endometrial explants. Our results indicate that mRNA and cytoplasmic proteins of RELA and CHUK exhibit constant levels in normal endometrium during the menstrual cycle. A dramatic increase (P!0.05) in NFKBIA mRNA expression, RELA nuclear presence and the mRNA and the protein of IL6 during late secretory phase was also observed in this tissue. By contrast, in eutopic endometrium from endometriosis patients, a decrease (P!0.05) in IL6 mRNA and protein (61%), NFKBIA mRNA (46%), p-NFKBIA/NFKBIA ratio (42%), RELA nuclear stromal (68%) and CHUK (48%) proteins were found exclusively during the late secretory phase compared with normal endometrium. In conclusion, the canonical activation of NFKB pathway is deregulated and may have reduced transcriptional function affecting NFKBIA and IL6 expression, genes related local proinflammatory processes. These molecular alterations observed during the late secretory phase in eutopic endometrium from endometriosis patients constitute a NFKB system dysfunction, suggesting that NFKB could be an important factor in endometriosis aetiology.

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Increased activation of nuclear factor-kappa B (NF-κB) in isolated peritoneal macrophages of patients with endometriosis

Cited by 84 publications

References 19 publications

Proangiogenic Tie2+ Macrophages Infiltrate Human and Murine Endometriotic Lesions and Dictate Their Growth in a Mouse Model of the Disease

Proangiogenic Tie2+ Macrophages Infiltrate Human and Murine Endometriotic Lesions and Dictate Their Growth in a Mouse Model of the Disease

Macrophages Are Alternatively Activated in Patients with Endometriosis and Required for Growth and Vascularization of Lesions in a Mouse Model of Disease

Nuclear factor κB pathway and interleukin-6 are affected in eutopic endometrium of women with endometriosis

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