Interleukin‐1β Down‐Regulates the Oxytocin Receptor in Cultured Uterine Smooth Muscle Cells

Rauk, Phillip N.; Friebe-Hoffmann, U

doi:10.1111/j.8755-8920.2000.430204.x

Cited by 46 publications

(32 citation statements)

References 18 publications

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“…In the human adrenal gland, however, glucocorticoids inhibit 17␣-hydroxylase activity, which is involved in dehydroepiandrosterone sulfate production [39]. Interleukin-1␤ (inflammatory cytokine) and oxytocin itself each reduced the OTR mRNA level in human myometrial cells and tissues [40][41][42][43][44]. Interleukin-6 had various effects on the expression of OTR mRNA.…”

Section: Discussionmentioning

confidence: 99%

Smoking Enhances Oxytocin-Induced Rhythmic Myometrial Contraction1

Egawa

Yasuda

Nakajima

et al. 2003

Biology of Reproduction

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Although smoking during pregnancy is one of the major risk factors of premature delivery, the underlying mechanism by which smoking causes premature delivery is unknown. In the present study, we examined the effects of smoking on uterine contractility induced by oxytocin and prostaglandin F(2alpha). Rats inhaled either cigarette smoke or room air from Day 14 to Day 16 of pregnancy through an inhalation apparatus for experimental animals (type "Hamburg II"). After the rats were killed on Day 17 of pregnancy, the uterine contractile sensitivity and activity on exposure to oxytocin or prostaglandin F2alpha were investigated. The expression levels of oxytocin-receptor mRNA and prostaglandin F(2alpha) receptor mRNA in the uterus were investigated by reverse transcription-polymerase chain reaction. The contractile activity was assessed as the contractile force and the frequency of rhythmic contractions of myometrial strips that were treated with oxytocin or prostaglandin F(2alpha). The contractile sensitivity to oxytocin was significantly higher in the smoking group than in the control group (P < 0.01). Although the contractile force of oxytocin-induced contractions did not differ between the smoking and control groups, the frequency of contractions was significantly higher in the smoking group than in the control group (P < 0.01). On the other hand, no significant differences were found in the contractile sensitivity and activity in response to prostaglandin F(2alpha) between the smoking and control groups. The expression of oxytocin-receptor mRNA in the myometrium was significantly increased in the smoking group compared with the control group (P < 0.01). However, no significant difference was found in the level of expression of prostaglandin F(2alpha)-receptor mRNA between the two groups. These results suggest that smoking during pregnancy increases the contractile sensitivity and activity of the myometrium in response to oxytocin by up-regulating the expression of oxytocin-receptor mRNA. The effects of smoking on the contractile sensitivity and activity of the myometrium in response to oxytocin may increase the risk of premature delivery in smokers.

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Section: Discussionmentioning

confidence: 99%

Smoking Enhances Oxytocin-Induced Rhythmic Myometrial Contraction1

Egawa

Yasuda

Nakajima

et al. 2003

Biology of Reproduction

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“…estrogen, progesterone), inflammatory cytokines (e.g. interleukin1b, interleukin-6), OT, and lactation suckling influence the expression of OTR at the mRNA or protein level (Phaneuf et al 1997, Phaneuf et al 1998, Fang et al 2000, Rauk & Friebe-Hoffmann 2000, Helmer et al 2002. However, the influence of these factors was limited in the present study using in vitro experiments under non-hormonal conditions.…”

Section: Discussionmentioning

confidence: 80%

Cigarette smoke extract enhances oxytocin-induced rhythmic contractions of rat and human preterm myometrium

Nakamoto¹,

Yasuda²,

Yasuhara³

et al. 2006

Reproduction

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Although smoking during pregnancy is a major risk factor for preterm delivery, the underlying mechanism by which smoking stimulates uterine contractions is still poorly understood. In the present study, we tried to clarify the effects of smoking on myometrial contractility induced by oxytocin (OT) using cigarette smoke extract (CSE). Myometrial strips, which were taken from the rat on day 16 of pregnancy, and from human preterm and term delivery groups, were incubated overnight with several doses of CSE at 37 8C under non-hormonal conditions. The uterine contractile sensitivity and activity (force and frequency) upon exposure to OT were investigated. Furthermore, the expression levels of oxytocin receptor (OTR) mRNA in the myometrial strips were investigated by real-time PCR. Contractile sensitivity to OT in the rat CSE (10 K7 pieces/ml) group was found to be significantly higher than in the control group (P!0.05). Contractile activity did not differ between the CSE and control groups. The expression levels of rat OTR mRNA in the CSE (10 K7 pieces/ml) group were significantly higher than in the control group (P!0.01). Similarly, in preterm myometrial strips, the expression levels of human OTR mRNA in the CSE (10 K7 pieces/ml) group were significantly higher than in the control group (P!0.05). These findings suggest that CSE directly increases the contractile sensitivity of preterm myometrium in response to OT by upregulating the expression of OTR mRNA and thereby increases the risk of preterm delivery in women, who smoke during pregnancy.

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“…Inositol triphosphate production and intracellular free calcium were reduced by 75% after IL-1 treatment. In comparison, the concentration of oxytocin receptors per cell was reduced by 90% after 24 h of IL-1 treatment [9]. This impairment in signaling appears to be solely due to a reduction in oxytocin receptors and not through changes in second-messenger signaling proteins.…”

Section: Discussionmentioning

confidence: 84%

“…Molnar et al [8] demonstrated that IL-1 treatment of myometrial tissues for a short duration increases arachidonic acid (AA) release and potentiates oxytocin-mediated contractility. In contrast, we have shown that prolonged exposure of myometrial cells to IL-1 results in down-regulation of the oxytocin receptor [9]. Following 24 h of IL-1 treatment, myometrial cells have 90% fewer oxytocin receptor binding sites.…”

Section: Introductionmentioning

confidence: 70%

Oxytocin Signaling in Human Myometrium Is Impaired by Prolonged Exposure to Interleukin-11

Rauk

Chiao

2000

Biology of Reproduction

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Intra-amniotic infection leads to preterm labor and is associated with the local release of inflammatory cytokines by fetal membranes, resulting in the production of uterotonic prostaglandins. Oxytocin, however, also plays a key role in the initiation of labor. Short-term exposure of myometrium to interleukin (IL)-1 enhances oxytocin signaling and contractility. With intrauterine infection, however, myometrium is exposed to inflammatory cytokines for prolonged periods. The present study was conducted to demonstrate that myometrial oxytocin signaling is significantly impaired following prolonged exposure to IL-1. Myometrial cells were treated with IL-1 for 24 h. Oxytocin-stimulated inositol trisphosphate (IP(3)) production was measured in tritiated myoinositol-loaded myometrial cells. Arachidonic acid (AA) release was measured in tritiated AA-loaded myometrial cells. Increases in intracellular calcium were measure with fluo-3. Prostaglandin (PG) F(2alpha) and 6-keto-PGF(1alpha) were measured by ELISA assay. Prolonged exposure of myometrial cells to IL-1 resulted in a significant reduction in oxytocin-mediated signaling as measured by IP(3) production and AA release, as well as a decrease in intracellular calcium. Prolonged exposure of myometrial cells to IL-1, however, resulted in enhanced PG release. Oxytocin may not contribute significantly to the labor-inducing action of IL-1 in the setting of preterm labor with prolonged infection.

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Interleukin‐1β Down‐Regulates the Oxytocin Receptor in Cultured Uterine Smooth Muscle Cells

Abstract: IL-1 down-regulates the uterine oxytocin receptor in a time- and dose-dependent fashion.

Cited by 46 publications

References 18 publications

Smoking Enhances Oxytocin-Induced Rhythmic Myometrial Contraction1

Smoking Enhances Oxytocin-Induced Rhythmic Myometrial Contraction1

Cigarette smoke extract enhances oxytocin-induced rhythmic contractions of rat and human preterm myometrium

Oxytocin Signaling in Human Myometrium Is Impaired by Prolonged Exposure to Interleukin-11

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