Inflammation promotes a cytokine response and disrupts the cervical epithelial barrier: a possible mechanism of premature cervical remodeling and preterm birth

Nold, Christopher; Anton, Lauren; Brown, Amy G.; Elovitz, Michal A.

doi:10.1016/j.ajog.2011.12.036

Cited by 62 publications

(66 citation statements)

References 34 publications

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“…The epithelial cell barrier disruption is enhanced following stimulation by a variety of inflammatory mediators including LPS [36], an endotoxin in the outer membrane of gram-negative bacteria that can stimulates mononuclear cells and neutrophils to secrete immunoregulatory and pro-allergic cytokines [37]. LPS herein aggravated the epithelium connection damage in HaCaT cells, being in agreement with a previous literature in Caco-2 cells [38].…”

Section: Discussionsupporting

confidence: 85%

Calycosin Suppresses Epithelial Derived Initiative Key Factors and Maintains Epithelial Barrier in Allergic Inflammation via TLR4 Mediated NF-κB Pathway

Wang

et al. 2017

Cell Physiol Biochem

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Background/Aims: Calycosin is a bioactive component of Astragali Radix, a Chinese herb for treating allergy. We have previously demonstrated that calycosin effectively inhibited allergic inflammation efficiently. The aim of this study was to explore the mechanism of calycosin on epithelial cells in allergic inflammation. Methods: An initial stage of atopic dermatitis (AD) model in which mice were just sensitized with FITC, was established in vivo and immortalized human keratinocytes (HaCaT cells) were utilized in vitro. Initiative key cytokines, TSLP and IL-33, were measured by ELISA, qPCR, immunofluorescence and Western blot. The junctions in epithelial cells were observed by electron microscopy and tight junctions (TJs) (Occludin and ZO-1) were assessed by Western blot and immunofluorescence. TLR4, MyD88, TAK1, TIRAP and NF-κB were measured by qPCR or Western blot. Results: The results showed that TSLP and IL-33 were inhibited significantly by calycosin in the initial stage of AD model. Simultaneously, calycosin attenuated the separated gap among the epithelial cells and increased the expression of TJs. TSLP/IL-33 and TJs were similarly affected in LPS-stimulated HaCaT cells in vitro. Meanwhile, calycosin not only inhibited the expressions of TLR4, MyD88, TAK1 and TIRAP, but also reduced NF-κB activation in vitro and in vivo. An NF-κB inhibitor enhanced the expressions of TJs and reduced that of TSLP/IL-33 in LPS-stimulated HaCaT cells. Conclusion: These results indicated that calycosin reduced the secretion of TSLP/IL-33 and attenuated the disruption of epithelial TJs by inhibiting TLR4 mediated NF-κB signaling pathway. These findings help to understand the beneficial effects of calycosin on AD, and to develop effective preventive or therapeutic strategies to combat this disease and other epithelial barrier deletion-mediated allergic diseases.

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Section: Discussionsupporting

confidence: 85%

Calycosin Suppresses Epithelial Derived Initiative Key Factors and Maintains Epithelial Barrier in Allergic Inflammation via TLR4 Mediated NF-κB Pathway

Wang

et al. 2017

Cell Physiol Biochem

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“…These findings suggest that the uterus and cervix are less structurally and functionally distinct than previously believed. Adding to the complexity, a layer of epithelial cells surrounds the cervical stroma, forming an active gateway and communication pathway to the external vaginal environment [12,13]. …”

Section: Cervical Tissue Architecturementioning

confidence: 99%

Cervical etiology of spontaneous preterm birth

Vink

Feltovich

2016

Seminars in Fetal and Neonatal Medicine

107

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SUMMARY The cervix functions as a barrier between the uterus and vagina and keeps the uterus closed until term so that the fetus can develop. For delivery the cervix must soften and dilate, and finally reconstitute to close the uterus. This complex process involves precisely timed activation of molecular and microstructural events. Spontaneous preterm birth (sPTB) can result from aberrant timing of these events in the cervix. Unfortunately, the pathophysiology of sPTB due to cervical causes remains unclear and thus our treatment options remain limited – even if all appropriate candidates were identified and correctly treated with currently available interventions, the rate of sPTB would only be reduced by 5%. Very recent molecular and microstructural investigation is challenging prevailing concepts about cervical remodeling in pregnancy. We believe that progress toward novel, targeted solutions for the diverse pathways to sPTB entails a paradigm shift in which the overlapping and complex interactions between the cervix, uterus, membranes, fetus, placenta, and surrounding (structural and molecular) environment are suitably honored.

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“…There is potential for differences in epithelial cell function between species as the human cervix is composed of glandular epithelia and a columnar and squamous epithelia that line the endocervix and ectocervix, respectively, while the mouse does not have glandular epithelia and the endocervix and ectocervix is primarily composed of squamous epithelia with a small region of columnar epithelia in the endocervix. Given the recent appreciation of the important roles of epithelia in the maintenance of barrier properties and immune surveillance in mouse and human, a better understanding of these differences is needed (Timmons et al 2010, Nold et al 2012.…”

Section: Relevance To Cervical Remodeling In Womenmentioning

confidence: 99%

Cervical remodeling in term and preterm birth: insights from an animal model

Mahendroo¹

2012

Reproduction

174

148

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Proper cervical function is essential for a normal pregnancy and birth to occur. Understanding the mechanisms that take place in normal pregnancy will allow a better comprehension of the complications involved in premature cervical remodeling and lead to better methods of diagnostics and prevention for preterm birth. Unfortunately, human samples are not easily available, and samples that are collected are often confounded by variations in timing and region of cervix from which sample is collected. Animal models, specifically the mouse, have facilitated a great deal of exploration into the mechanisms of cervical function and pathways of preterm birth. This review highlights some of the groundbreaking discoveries that have arisen from murine research including 1) the identification of early pregnancy changes in collagen fibril processing and assembly that result in progressive modifications to collagen architecture with subsequent loss of tissue stiffness during pregnancy, 2) the determination that immune cells are not key to cervical ripening at term but have diverse phenotypes and functions in postpartum repair, and 3) the finding that the process of preterm cervical ripening can differ from term ripening and is dependent on the etiology of prematurity. These findings, which are relevant to human cervical biology, provide new insights that will allow targeted studies on the human cervix as well as identify potential biomarkers for early detection of premature cervical ripening and development of improved therapies to prevent premature ripening of the cervix and subsequent preterm birth.

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Inflammation promotes a cytokine response and disrupts the cervical epithelial barrier: a possible mechanism of premature cervical remodeling and preterm birth

Cited by 62 publications

References 34 publications

Calycosin Suppresses Epithelial Derived Initiative Key Factors and Maintains Epithelial Barrier in Allergic Inflammation via TLR4 Mediated NF-κB Pathway

Calycosin Suppresses Epithelial Derived Initiative Key Factors and Maintains Epithelial Barrier in Allergic Inflammation via TLR4 Mediated NF-κB Pathway

Cervical etiology of spontaneous preterm birth

Cervical remodeling in term and preterm birth: insights from an animal model

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