Dienogest inhibits nerve growth factor expression induced by tumor necrosis factor-α or interleukin-1β

Mita, Shizuka; Shimizu, Yutaka; Sato, Ayumi; Notsu, Tatsuto; Imada, Kazunori; Kyo, Satoru

doi:10.1016/j.fertnstert.2013.10.038

Cited by 35 publications

(20 citation statements)

References 53 publications

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“…Recently, studies have demonstrated that small interfering RNA-mediated silencing of NGF reduced nerve fiber density and improved hyperalgesia in a rat model of endometriosis (38), the same authors also described growth suppression of ectopic endometriotic implants, suggesting a role for NGF beyond regulation of neurogenesis in the condition. TNF␣-and IL-1␤-induced NGF production by endometrial epithelial cells can be inhibited by the progestogen Dienogest (39), which further supports our observation of estrogen-dependent up-regulation of NGF. VEGF-A is thought to be a key regulator of angiogenesis in endometriosis; gene expression levels are significantly higher in the eutopic endometrium of women with endometriosis compared with those without and also in endometriosis lesions compared with the peritoneum (40).…”

Section: Discussionsupporting

confidence: 89%

Estrogen Receptor (ER) Agonists Differentially Regulate Neuroangiogenesis in Peritoneal Endometriosis via the Repellent Factor SLIT3

et al. 2014

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Endometriosis is an estrogen-dependent neurovascular disorder characterized by growth of endometrial tissue (lesions) outside the uterine cavity. Patients suffer chronic pelvic pain, and it has been proposed that co-recruitment of nerves/blood vessels (neuroangiogenesis) into the lesions is fundamental to the development of painful symptoms. We hypothesized that estrogen-dependent regulation of axonal guidance molecules of the SLIT/ROBO (Roundabout) family could play a role in neuroangiogenesis occurring in endometriosis lesions found on the peritoneal wall. In tissue samples from human patients and a mouse model of endometriosis, concentrations of mRNA encoded by SLIT3 were significantly higher in lesions than normal peritoneum. Estrogen regulation of SLIT3 was investigated using 17β-estradiol and selective agonists for each subtype of estrogen receptor (ER) (ERα agonist, 4,4',4″-(4-propyl-(1H)-pyrazole-1,3,5-tryl) trisphenol; ERβ agonist, 2,3-bis(4-hydroxy-phenyl)-propionitrile [DPN]). In mice, DPN (EC50 0.85) increased Slit3 mRNA concentrations compared with hormone-depleted and 17β-estradiol-treated (EC50 0.1) animals and decreased the density of nerves but not vessels in endometriosis lesions. SLIT3 mRNA concentrations were increased in DPN-treated human endometrial endothelial cells and in 4,4',4″-(4-propyl-(1H)-pyrazole-1,3,5-tryl) trisphenol-treated (EC50 200) rat dorsal root ganglia neurons. Functional assays (neurite outgrowth, network formation) revealed that SLIT3 promotes angiogenesis but decreases neurogenesis. In conclusion, these data suggest that estrogen-dependent expression of SLIT3 may play a key role in regulating nerve-vessel interactions within the complex microenvironment of endometriosis lesions.

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Section: Discussionsupporting

confidence: 89%

Estrogen Receptor (ER) Agonists Differentially Regulate Neuroangiogenesis in Peritoneal Endometriosis via the Repellent Factor SLIT3

et al. 2014

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“…The elevated levels of NGF in inflammatory reactions have been indicated to result in the aggravation of pain (41). Previous studies have indicated that proinflammatory cytokines (IL-1β, TNF-α) are closely associated with NGF, and promote an increase in the levels of NGF (42)(43)(44). In addition, NGF may act on proinflammatory cytokines in turn (45).…”

Section: Discussionmentioning

confidence: 99%

Treatment with olopatadine and naphazoline hydrochloride reduces allergic conjunctivitis in mice through alterations in inflammation, NGF and VEGF

Quan

2016

Molecular Medicine Reports

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The aim of the current study was to investigate whether olopatadine and naphazoline hydrochloride reduce allergic conjunctivitis in mice through alterations in inflammation, NGF and VEGF. An allergic conjunctivitis mouse model was established using histamine or an antigen (ovalbumin), following which mice were treated with 1% olopatadine solution and/or 0.2 mg/ml of naphazoline hydrochloride. Histamine or antigen‑induced conjunctival vascular hyperpermeability was examined and the levels of inflammatory factors, cytokines, IgE, GMCSF and NGF were analyzed using ELISA in antigen‑induced conjunctival vascular hyperpermeability mice. In addition, VEGF protein expression was measured using western blotting in antigen‑induced mice. The results indicated that olopatadine and naphazoline hydrochloride significantly suppressed conjunctival dye leakage in mice with histamine or antigen‑induced conjunctival vascular hyperpermeability. In addition, treatment with olopatadine and naphazoline hydrochloride was able to reduce the levels of inflammatory factors (TNF‑α, IL‑1β and IL‑6), cytokines (IFN‑γ and IL‑4), IgE, GMCSF, and NGF in antigen‑induced conjunctival vascular hyperpermeability mice. The protein expression levels of VEGF in antigen‑induced conjunctival vascular hyperpermeability mice were reduced following treatment with olopatadine and naphazoline hydrochloride. These results suggest that treatment with olopatadine and naphazoline hydrochloride reduces conjunctivitis in mice via effects on inflammation, NGF and VEGF.

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“…The PF of women with peritoneal endometriotic lesions has a significantly higher NGF concentration, compared with women without endometriosis [35]. TNFa and IL-1b treatment of human endometrial epithelial cells (hEECs) also induces NGF secretion [36]. However, NGF mRNA expression in whole endometrioma lesions and pain are not correlated [37], although women with severe pain were more likely to have high PF NGF concentrations [32].…”

Section: Endometriosis-associated Inflammationmentioning

confidence: 99%

Inflammation and nerve fiber interaction in endometriotic pain

McKinnon

Bertschi

Bersinger

et al. 2015

Trends in Endocrinology & Metabolism

169

130

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Dienogest inhibits nerve growth factor expression induced by tumor necrosis factor-α or interleukin-1β

Cited by 35 publications

References 53 publications

Estrogen Receptor (ER) Agonists Differentially Regulate Neuroangiogenesis in Peritoneal Endometriosis via the Repellent Factor SLIT3

Estrogen Receptor (ER) Agonists Differentially Regulate Neuroangiogenesis in Peritoneal Endometriosis via the Repellent Factor SLIT3

Treatment with olopatadine and naphazoline hydrochloride reduces allergic conjunctivitis in mice through alterations in inflammation, NGF and VEGF

Inflammation and nerve fiber interaction in endometriotic pain

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