CXCL8 enhances proliferation and growth and reduces apoptosis in endometrial stromal cells in an autocrine manner via a CXCR1-triggered PTEN/AKT signal pathway

Li, Ming‐Qing; Luo, Xuezhen; Meng, Yuguang; Mei, Jie; Zhu, Xiao‐Yong; Jin, Liping; Li, Da‐Jin

doi:10.1093/humrep/des132

Cited by 65 publications

(53 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The shift toward estrogen dominance induces these factors that promote inflammation, angiogenesis, cell proliferation and immunosuppression. IL-17-induced IL-8 has been shown to target the PTEN/AKT signaling pathway which is aberrantly activated in endometriosis (96). IL-17 also induces the inflammatory cytokine IL-6 (61), that is elevated in the endometrium of endometriosis patients (97, 98).…”

Section: Endometriosis and Inflammationmentioning

confidence: 99%

Endometrial receptivity in the eutopic endometrium of women with endometriosis: it is affected, and let me show you why

Lessey¹,

Kim²

2017

Fertility and Sterility

216

158

View full text Add to dashboard Cite

The endometrium maintains complex controls on proliferation and apoptosis as part of repetitive menstrual cycles that prepare the endometrium for the window of implantation and pregnancy. The reliance on inflammatory mechanisms for both implantation and menstruation, creates the opportunity in the setting of endometriosis for the establishment of chronic inflammation that is disruptive to endometrial receptivity, causing both infertility and abnormal bleeding. Clinically, there can be little doubt that the endometrium of women with endometriosis is less receptive to embryo implantation, and strong evidence exists to suggests that endometrial changes are associated with decreased cycle fecundity as a result of this disease. Here we provide unifying concepts regarding those changes and how they are coordinated to promote progesterone resistance and estrogen dominance through aberrant cell signaling pathways and reduced expression of key homeostatic proteins in eutopic endometrium of women with endometriosis.

show abstract

Section: Endometriosis and Inflammationmentioning

confidence: 99%

Endometrial receptivity in the eutopic endometrium of women with endometriosis: it is affected, and let me show you why

Lessey¹,

Kim²

2017

Fertility and Sterility

216

158

View full text Add to dashboard Cite

show abstract

“…IL-8 signals primarily through the receptors CXCR1 and CXCR2, present in various types of normal as well as cancerous cells (Gales et al, 2013). The enzyme PI3-kinase (PI3K) is a principal effector of IL-8-mediated chemotaxis in neutrophils (Lane et al, 2006; Li et al, 2012). Recent advances reveal IL-8 signaling as a potential key to targeting breast cancer stem cells (Singh et al, 2013), suggesting that IL-8 and its receptors may be attractive targets for cancer therapy.…”

Section: Introductionmentioning

confidence: 99%

IL-8 signaling is up-regulated in alcoholic hepatitis and DDC fed mice with Mallory Denk Bodies (MDBs) present

Liu

French

Nelson

et al. 2015

Experimental and Molecular Pathology

View full text Add to dashboard Cite

Chemokines and their receptors are involved in oncogenesis and in tumor progression, invasion, and metastasis. Various chemokines also promote cell proliferation and resistance to apoptosis of stressed cells. The chemokine CXCL8, also known as interleukin-8 (IL-8), is a proinflammatory molecule that has functions within the tumor microenvironment. Deregulation of IL-8 signaling is shown to play pivotal roles in tumorigenesis and progression. Mallory-Denk Bodies (MDBs) are prevalent in various liver diseases including alcoholic hepatitis (AH) and are formed in mice livers by feeding DDC. By comparing AH livers where MDBs had formed with normal livers, there were significant changes of IL-8 signaling by RNA sequencing (RNA-Seq) analyses. Real-time PCR analysis of CXCR2 further shows a 6-fold up regulation in AH livers and a 26-fold up regulation in the livers of DDC re-fed mice. IL-8 mRNA was also significantly up regulated in AH livers and DDC re-fed mice livers. This indicates that CXCR2 and IL-8 may be crucial for liver MDB formation. MDB containing balloon hepatocytes in AH livers had increased intensity of staining of the cytoplasm for both CXCR2 and IL-8. Over expression of IL-8 leads to an increase of the mitogen activated protein kinase (MAPK) cascade and exacerbates the inflammatory cycle. These observations constitute a demonstration of the altered regulation of IL-8 signaling in the livers of AH and mice fed DDC where MDBs formed, providing further insight into the mechanism of MDB formation mediated by IL-8 signaling in AH.

show abstract

“…In the current study, the effects of CXCL-8 on HUVEC cells were blocked by Akt inhibitors, resulting in reduced proliferation and migration, thus suggesting that Akt may serve a key role in the process of HUVEC migration (53). Although the PI3K/Akt and JAK/STAT3 signal transduction pathways are involved in the effects of CXCL-8 in vascular endothelial cells (53), the effects of CXCL-8 may also be transduced by extracellular signal-regulated kinase and other signaling molecules, though the associated mechanisms warrant further investigation (53,54).…”

Section: Discussionmentioning

confidence: 48%

C-X-C motif chemokine ligand 8 promotes endothelial cell homing via the Akt-signal transducer and activator of transcription pathway to accelerate healing of ischemic and hypoxic skin ulcers

Shen

Zhang

et al. 2017

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. C-X-C motif chemokine ligand 8 (CXCL-8) promotes cell homing and angiogenesis. However, under hypoxic conditions, the role of CXCL-8 in the homing of human umbilical vein endothelial cells (HUVECs), and its effect on the healing of skin ulcers caused by ischemia and hypoxia remain unknown. In the current study, assays measuring cell proliferation, in vitro angiogenesis and cell migration were performed to evaluate alterations in the proliferation, angiogenic capacity and chemotaxis of HUVECs treated with CXCL-8 protein and/or an Akt inhibitor (AZD5363 group) under hypoxic conditions. Changes in the levels of Akt, signal transducer and activator of transcription 3 (STAT3), vascular endothelial growth factor (VEGF), malondialdehyde (MDA) and total-superoxide dismutase (total-SOD) were also detected by western blotting and ELISA. In addition, in vivo experiments were performed using a skin ulcer model in mice. Ischemic and hypoxic skin ulcers were created on the thighs of C57BL/6J mice, and the effects of CXCL-8 and HUVEC transplantation on the healing capacity of skin ulcers was determined by injecting mice with HUVECs and/or CXCL-8 recombinant protein (CXCL-8, HUVEC and HUVEC + CXCL-8 groups). Vascular endothelial cell homing, changes in vascular density and the expression of VEGF, SOD, EGF and MDA within the ulcer tissue were subsequently measured. In vitro experiments demonstrated that HUVEC proliferation, migration and tube forming capacity were significantly increased by CXCL-8 under hypoxic conditions. Additionally, levels of VEGF, MDA and SOD were significantly higher in the CXCL-8 group, though were significantly decreased by the Akt and STAT3 inhibitors. In vivo experiments demonstrated that the expression of VEGF, total-SOD and EGF proteins were higher in the skin ulcer tissue of mice treated with CXCL-8 + HUVEC, relative to mice treated with HUVECs alone. Furthermore, vascular endothelial cell homing and vascular density were significantly increased in the CXCL-8 + HUVEC group, indicating that combined use of HUVECs and CXCL-8 may promote the healing of ischemic skin ulcers. The present results demonstrate that CXCL-8 may stimulate vascular endothelial cells to secrete VEGF, SOD and other cytokines via the Akt-STAT3 pathway, which in turn serves a key regulatory role in the recruitment of vascular endothelial cells, reduction of hypoxia-related injury and promotion of tissue repair following hypoxic/ischemic injury.

show abstract

CXCL8 enhances proliferation and growth and reduces apoptosis in endometrial stromal cells in an autocrine manner via a CXCR1-triggered PTEN/AKT signal pathway

Abstract: This study suggests that CXCL8 and CXCR1 are involved in the pathogenesis of endometriosis by up-regulating proliferation and growth and restricting apoptosis in ESCs by activating the PTEN/Akt pathway and mediating the expression of survivin and Bcl-2.

Cited by 65 publications

References 33 publications

Endometrial receptivity in the eutopic endometrium of women with endometriosis: it is affected, and let me show you why

Endometrial receptivity in the eutopic endometrium of women with endometriosis: it is affected, and let me show you why

IL-8 signaling is up-regulated in alcoholic hepatitis and DDC fed mice with Mallory Denk Bodies (MDBs) present

C-X-C motif chemokine ligand 8 promotes endothelial cell homing via the Akt-signal transducer and activator of transcription pathway to accelerate healing of ischemic and hypoxic skin ulcers

Contact Info

Product

Resources

About