Corticotropin Releasing Hormone Modulates Endotoxin-Induced Inflammatory Cytokine Expression in Human Trophoblast Cells

Wang, W.; Nan, Xunyi; Ji, Ping; Dow, Kimberly

doi:10.1016/j.placenta.2007.04.007

Cited by 27 publications

(11 citation statements)

References 44 publications

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“…Secretion of p CRH is directly stimulated by pro-inflammatory cytokines such as IL -1 and microbial antigens (84). CRH, in turn, has been shown to have a pro-inflammatory effect in the periphery (85, 86), and increased levels of p CRH have been associated with intra-amniotic infection (72, 87). Moreover, previous studies of non-pregnant CT+ women have reported they exhibit an increased inflammatory status (88–90).…”

Section: Discussionmentioning

confidence: 99%

Maternal Exposure to Childhood Trauma Is Associated During Pregnancy With Placental-Fetal Stress Physiology

Moog

Buß

Entringer

et al. 2016

Biological Psychiatry

109

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Background The effects of exposure to childhood trauma (CT) may be transmitted across generations, however the time period(s) and mechanism(s) have yet to be clarified. We address the hypothesis that intergenerational transmission may begin during intrauterine life via the effect of maternal CT exposure on placental-fetal stress physiology, specifically placental corticotrophin-releasing hormone (pCRH). Methods The study was conducted in a sociodemographically-diverse cohort of 295 pregnant women. CT exposure was assessed using the Childhood Trauma Questionnaire. Placental CRH concentrations were quantified in maternal blood collected serially over the course of gestation. Linear mixed effects and Bayesian piecewise linear models were employed to test hypothesized relationships. Results Maternal CT exposure (CT+) was significantly associated with pCRH production. Compared to non-exposed women, CT+ was associated with an almost 25% increase in pCRH towards the end of gestation, and the pCRH trajectory of CT+ women exhibited an approximately two-fold steeper increase after the pCRH inflection point at 19 wks gestation. Conclusions To the best of our knowledge, this finding represents the first report linking maternal CT exposure with placental-fetal stress physiology, thus identifying a potential novel biological pathway of intergenerational transmission that may operate as early as during intrauterine life.

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Section: Discussionmentioning

confidence: 99%

Maternal Exposure to Childhood Trauma Is Associated During Pregnancy With Placental-Fetal Stress Physiology

Moog

Buß

Entringer

et al. 2016

Biological Psychiatry

109

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“…Thus, a more complex picture is likely to emerge regarding the role of chemokines in trophoblast migration. Unstimulated HTR-8/SVneo cells have already been shown to produce IL8 at the mRNA and protein levels (Svinarich et al 1996, Chou et al 2006, and this was increased by treatment with lipopolysaccharide (Svinarich et al 1996) and was augmented further by pre-exposure to CRH (Wang et al 2007). The autocrine action of IL8 was tested by neutralization in HTR-8/SVneo cells.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-8 (CXCL8) stimulates trophoblast cell migration and invasion by increasing levels of matrix metalloproteinase (MMP)2 and MMP9 and integrins α5 and β1

Jovanović¹,

Stefanoska²,

Radojčić³

et al. 2010

Reproduction

198

132

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Interleukin-8 (IL8/CXCL8) is present in decidua and trophoblast, which also expresses the IL8 receptors, CXCR1 and CXCR2. IL8 was shown to stimulate trophoblast migration. Matrix metalloproteinase (MMP)2, MMP9, and integrins a 5 b 1 and a 1 b 1 were found to play important roles in trophoblast invasion. We hypothesized that IL8 would increase this cell migration and invasion by HTR-8/SVneo cells through the activity of MMPs and integrins. Isolated first trimester of pregnancy cytotrophoblast (CT) and HTR-8/SVneo cell line were used. Migration was studied by monolayer wounding test, and invasion by Matrigel invasion test. The effects of IL8 on MMPs and integrin subunit expression were determined in HTR-8/SVneo cells by gelatin zymography and western blot respectively. The results that were obtained showed that exogenous IL8 stimulated HTR-8/SVneo cell migration and invasion. MMP2 and MMP9 levels were stimulated to 182% (P!0.01) and 134% (P!0.01) respectively. Integrin a 5 expression was increased to 119% (P!0.05) and integrin b 1 expression to 173% (P!0.001) of the control values. The data that were obtained show for the first time the sensitivity of the HTR-8/SVneo cells, in addition to isolated first trimester CT, to IL8. Exogenous IL8/CXCL8 increased trophoblast cell migration and invasion, which may be partly attributable to stimulation of MMP2 and MMP9 levels and an increase in integrins. HTR-8/SVneo cell viability and proliferation were also increased.

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“…The fact that CRH and its receptors are localized in the cervix ( Klimaviciute et al ., 2006 ) and that it has an effect on IL-8 secretion from cervical fibroblasts points towards the possible role of CRH in the process of the cervical ripening. Several studies have shown that CRH can stimulate the production of proinflammatory cytokines in different cells ( Angioni et al ., 1993 ; Yang et al ., 2005 ; Wang et al ., 2007 ), although some studies present contradicting results ( Angioni et al ., 1993 ; Sehringer et al ., 2000 ). The possible mechanism by which CRH induces IL-8 production in the cervical fibroblasts could be a selective activation of the p38/MAPK signaling pathway ( Wang et al ., 2007 ).…”

Section: Discussionmentioning

confidence: 99%

Different secretion patterns of matrix metalloproteinases and IL-8 and effect of corticotropin-releasing hormone in preterm and term cervical fibroblasts

Dubicke

Åkerud

Sennström

et al. 2008

Molecular Human Reproduction

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The aims of the present study were to compare the levels of mRNA and protein expression of matrix metalloproteinase (MMP)-1, -3, -8 and -9 in human cervical tissue in preterm and term labor as well as not in labor and to determine if corticotropin-releasing hormone (CRH) has an effect on MMP-1, -3 and interleukin (IL)-8 secretion in both preterm and term cervical fibroblasts. Cervical biopsies were taken from 60 women: 18 at preterm labor, 7 at preterm not in labor, 18 at term labor and 17 at term not in labor. ELISA and Immulite were used for protein and real-time RT–PCR for mRNA analysis. Cervical fibroblast cultures were incubated for 18 h with different CRH concentrations (10−13–10−6 M). The mRNA expression of MMP-1, -3 and -9 was higher in laboring groups compared with term not in labor. Protein levels of MMP-8 and -9 were higher in term in labor group compared with non-laboring groups. There were no significant differences in mRNA and protein expression between the preterm and respective term control groups. CRH significantly increased secretion of IL-8 in preterm and term cervical fibroblasts compared with controls. The secretion of IL-8 and MMP-1 was significantly higher and MMP-3 secretion lower in preterm cervical fibroblasts. In conclusion, cervical ripening at preterm seems to be a similar inflammatory process as at term with CRH involved. However, preterm and term cervical fibroblasts might have different phenotypes based on different secretion patterns of IL-8, MMP-1 and MMP-3.

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Corticotropin Releasing Hormone Modulates Endotoxin-Induced Inflammatory Cytokine Expression in Human Trophoblast Cells

Cited by 27 publications

References 44 publications

Maternal Exposure to Childhood Trauma Is Associated During Pregnancy With Placental-Fetal Stress Physiology

Maternal Exposure to Childhood Trauma Is Associated During Pregnancy With Placental-Fetal Stress Physiology

Interleukin-8 (CXCL8) stimulates trophoblast cell migration and invasion by increasing levels of matrix metalloproteinase (MMP)2 and MMP9 and integrins α5 and β1

Different secretion patterns of matrix metalloproteinases and IL-8 and effect of corticotropin-releasing hormone in preterm and term cervical fibroblasts

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