Estrogen Inhibits Interleukin-18 mRNA Expression in the Mouse Uterus

Murakami, Yousuke; Otsuki, Mariko; Kusumoto, Kenji; Tanaka, Sakae; Takahashi, Sumio

doi:10.1262/jrd.17029

Cited by 22 publications

(17 citation statements)

References 39 publications

(47 reference statements)

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“…18Rβ subunits, which constitute functional IL-18 receptors, is highly probable in uteri, although we did not analyze the expression of IL-18Rα and IL-18Rβ proteins. We recently demonstrated that IL-18 mRNA is present in mouse uteri [10,11]. Taken together, these observations suggest the presence of the IL-18 system in the mouse uterus.…”

Section: Discussionmentioning

confidence: 55%

“…These findings indicate that IL-18Rα gene expression is regulated by estrogen and progesterone. Our previous study also revealed that IL-18 mRNA expression was decreased by estrogen and progesterone [11]. Therefore, it is possible that the physiological actions of IL-18 may be inhibited by sex steroid hormones, and IL-18 may exert its actions under the conditions of low circulating levels of steroid hormones.…”

Section: Discussionmentioning

confidence: 92%

“…In addition, IL-18 is expressed in reproductive organs such as the uterus in humans [8], and the ovaries in mice [9]. Our recent study revealed that IL-18 mRNA is expressed in the mouse endometrium and that its expression is regulated by estrogen [10,11]. In situ hybridization analysis demonstrated that IL-18 mRNA is mainly detected in glandular epithelial cells and stromal cells in the adult mouse uterus [10].…”

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confidence: 96%

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Expression of Interleukin-18 Receptor mRNA in the Mouse Endometrium

Otsuki

Kusumoto

Murakami

et al. 2007

Journal of Reproduction and Development

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Abstract. ) is a proinflammatory cytokine involved in chronic inflammation, autoimmune diseases, and a variety of cancers, and is expressed in mouse uteri. Our previous study suggested that IL-18 acts as a paracrine factor, regulating endometrial function. To elucidate the physiological roles of IL-18 in the mouse endometrium, the expression of the IL-18 receptor (IL-18R) α subunit was analyzed. IL-18Rα mRNA was expressed in several mouse organs in addition to the endometrium. In situ hybridization analysis using a biotin-labeled mouse IL-18Rα riboprobe demonstrated that IL-18Rα mRNA expression was detected in glandular epithelial cells, stromal cells around uterine glands, and myometrial cells in the mouse uterus, suggesting that these cells are targets for IL-18. The uterine IL-18Rα mRNA expression level changed with the estrous cycle. The uterine IL-18Rα mRNA levels of estrous mice were higher than those of diestrous mice. In addition, the IL-18Rα mRNA levels in uteri at 3 and 14 days after ovariectomy were higher than those at diestrus and decreased following treatment with estradiol-17β or progesterone. These findings suggest that IL-18Rα gene expression is regulated by estrogen and progesterone and that the uterine IL-18 system is involved in the regulation of uterine functions in a paracrine manner.

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Section: Discussionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 92%

mentioning

confidence: 96%

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Expression of Interleukin-18 Receptor mRNA in the Mouse Endometrium

Otsuki

Kusumoto

Murakami

et al. 2007

Journal of Reproduction and Development

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“…Hormonal administration as a consequence of ovarian hyperstimulation will increase the cytokine depletion, since endometrial exposure to a high concentration of oestrogens significantly decreases endometrial IL-18 expression (Ledee et al, 2006). A negative impact of oestrogens on IL-18 expression has been also reported in mice and pigs (Ashworth et al, 2010;Murakami et al, 2005).…”

Section: The Role Of Endometrial Tumor Necrosis Factor-like Weak Indumentioning

confidence: 99%

New pre-conception immune biomarkers for clinical practice: interleukin-18, interleukin-15 and TWEAK on the endometrial side, G-CSF on the follicular side

Lédée

Petitbarat

Rahmati

et al. 2011

Journal of Reproductive Immunology

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a b s t r a c tIdentification of biomarkers of optimal uterine receptivity to the implanting embryo as well as biomarkers of oocyte competence would undoubtedly improve the efficiency of assisted reproductive technology (ART). Expression of IL-15 and IL-18 has been shown to be different in patients with failed implantation after IVF/ICSI compared with fertile controls and both correlate with local uNK (CD56+) recruitment and angiogenesis. Tumor necrosis factor weak inducer of apoptosis (TWEAK) has been described in mice as a potent early immune regulator able to protect the conceptus. The results of our studies in human suggest that TWEAK modulates the IL-18 related cytotoxicity of uNK cells. Quantification of IL-18, TWEAK and IL-15 mRNA expression by real-time PCR in endometrial tissue collected in midluteal phase of non-conception cycles allowed documentation of physiological events that occur at the time of uterine receptivity. Such information may be useful for the physician especially in patients where embryos fail to implant. Cytokine quantification may assist in understanding the mechanisms leading to repeated IVF/ICSI failure: either depletion of cytokines necessary for the apposition-adhesion, or an excess of cytokines leading to local cytotoxicity, may impair the implantation of the embryo. Other new data suggest that a pre-conception dialogue mediated by the oocyte and the follicular fluid and the oocyte may contribute to later implantation success. Follicular concentration of G-CSF appears as a useful biomarker of oocyte competence before fertilization. Moreover both in human and animal models, evidence of a role of the endometrium as a biosensor of the embryo is emerging.

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“…In addition, it has been reported that estrogens prevent the expression of IL-18 in mouse uterus. 17) On the other hand, we also found that excessive IFN-γ via IL-18 results in cataract development. 18,19) From these reports, it is possible that IL-18 levels are also increased in the lenses of postmenopausal women, and that enhanced IFN-γ via IL-18 may lead to the formation and progression of cataracts.…”

mentioning

confidence: 52%

Increased Expression of Interleukin-18 in Lenses of Ovariectomized Rats

Nagai

Ogata

Kawasaki

et al. 2016

Biological & Pharmaceutical Bulletin

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Previous studies showed an increased prevalence of cataracts in postmenopausal women. In this study, we investigated changes in the levels of calcium ion (Ca 2 ) and interleukin (IL)-18, which are factors in cataract development, in the lenses of ovariectomized (OVX) rats, a model of postmenopausal woman. Although the Ca 2 content in the blood of OVX rats increased 1 month after ovariectomy and subsequently decreased, the Ca 2 content in the lenses was unchanged in OVX rats 1-3 months after ovariectomy. The Ca 2 -ATPase activity in the lenses of OVX rats peaked 1 month after ovariectomy, and the behavior of Ca 2 -ATPase activity in lenses of OVX rats was similar to that of the Ca 2 concentration in the blood. It is possible that hypercalcemia increases the Ca 2 inflow into the lens; however, the enhanced Ca 2 -ATPase activity prevents the Ca 2 level from rising. On the other hand, we found that the levels of both IL-18 and interferon (IFN)-γ in the lenses of OVX rats were significantly increased as compared with the lenses of sham (control) rats during the period 1-3 months after surgery. These results suggest that the expression of IFN-γ via IL-18 in the lenses of OVX rats is induced by ovariectomy, and that excessive IL-18 and IFN-γ production in the lenses may be related to cataract development in postmenopausal women. These findings support those of previous studies that assessed lens opacification in postmenopausal women.Key words interleukin-18; lens; ovariectomized rat; interferon-γ; calcium Cataracts are defined as any alteration in the optical homogeneity of the lens or a decrease in its transparency. 1,2) Exposure to reactive oxygen species, interleukin (IL) or interferon (IFN)-γ induced by UV in sunlight are considered to result in a breakdown of lens homeostasis, resulting in an elevation in the calcium ion (Ca 2+ ) content of the lens. This elevated Ca 2+ content has been deduced to activate calpain, a Ca 2+ -dependent protease, leading to an increased degradation of lens proteins, such as crystallin proteins, resulting in an opaque lens.3,4) Therefore, the regulation of Ca 2+ levels in lens is important to prevent opacification. Previous studies have shown an increased prevalence of cataracts in postmenopausal women, and estrogen has been reported to be effective in preventing age-related cataracts. [5][6][7][8] Estrogen is a hormone that participates in regulating calcium (Ca) levels in the body, and postmenopausal women experience a drop in estrogen secretion. Bone resorption is regulated by estrogen, and a decrease in estrogen level leads to a decrease in vitamin D. Since vitamin D enhances Ca 2+ absorption from the small intestine, [9][10][11][12] postmenopausal women are at greater risk of osteoporosis and hypercalcemia/ hypocalcemia via the dysfunction in Ca 2+ regulation due to a chronic reduction in circulating estrogen levels.9-12) This reduced capacity to regulate Ca 2+ levels may be related to the onset of cataracts via an increase in Ca 2+ levels in the lens. Estrogens are also kno...

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Estrogen Inhibits Interleukin-18 mRNA Expression in the Mouse Uterus

Cited by 22 publications

References 39 publications

Expression of Interleukin-18 Receptor mRNA in the Mouse Endometrium

Expression of Interleukin-18 Receptor mRNA in the Mouse Endometrium

New pre-conception immune biomarkers for clinical practice: interleukin-18, interleukin-15 and TWEAK on the endometrial side, G-CSF on the follicular side

Increased Expression of Interleukin-18 in Lenses of Ovariectomized Rats

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