Signaling via the type I IL-1 and TNF receptors is necessary for bacterially induced preterm labor in a murine model

Hirsch, Emmet; Filipovich, Yana; Mahendroo, Mala

doi:10.1016/j.ajog.2005.11.004

Cited by 117 publications

(91 citation statements)

References 41 publications

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“…macrophage) can have diverse phenotypes dependent on the microenvironment limits the conclusions that can be drawn from these reports. Evidence from our group and others suggest that activation of immune cells is not required for physiological ripening at term (Hirsch et al 2006, Timmons & Mahendroo 2006, Gonzalez et al 2009, Timmons et al 2009). During ripening there is an influx of monocytes into the cervix that are dependent on the loss of P 4 function.…”

Section: Cervical Ripening and Dilation: Accelerated Phases Of Remodementioning

confidence: 99%

“…This knowledge emphasizes the need to define the molecular processes that drive term and preterm cervical remodeling. While preterm birth was once considered an acceleration of the normal physiological process, evidence to support diverse mechanisms by which preterm birth can occur is mounting (Gross et al 2000, Hirsch et al 2006. Recent studies using two established mouse models of preterm birth have provided novel insights into distinct processes by which cervical ripening can occur.…”

Section: Premature Cervical Ripeningmentioning

confidence: 99%

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

Mahendroo¹

2012

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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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Section: Cervical Ripening and Dilation: Accelerated Phases Of Remodementioning

confidence: 99%

Section: Premature Cervical Ripeningmentioning

confidence: 99%

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

Mahendroo¹

2012

Reproduction

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174

148

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“…Each group was treated with 2 consecuflammation in the birth process. Other evidence is from studies using mice deficient in receptors for classical inflammatory factors, such as interleukin (IL)-1α and tumor necrosis factor (TNF)-α, or those showing that mice treated with blockers of these receptors are more resistant to the toll-like receptor agonist (lipopolysaccharide, LPS)-induced preterm birth (14,15). It is important to note that the association of inflammation in normal uterine cervical remodeling and birth has recently been disputed by some studies (5,40,41).…”

Section: Methodsmentioning

confidence: 99%

“…Animal studies have shown that mice with deletions in both IL-1 and TNF-α receptors have a significantly reduced susceptibility to bacteria-induced preterm labor (14). We also know that the inflammatory signaling pathway is extensive and is notoriously redundant.…”

Section: Fig 1 Optimization Of Vegf Treatment In Mice Uterine Cervixmentioning

confidence: 99%

Vascular endothelial growth factor induces mRNA expression of pro-inflammatory factors in the uterine cervix of mice

Nguyen¹,

Minkiewicz²,

McCabe³

et al. 2012

Biomed. Res.

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Inflammation is believed to play a role in uterine cervical remodeling and infection-induced preterm labor. One of the distinct features of remodeling uterine cervix is presence of prominent vascular events, such as angiogenesis, vasodilation, and vascular permeability. Although the functional significance of these features is not yet clear, we know that in most tissue types, vascular remodeling is intricately intertwined with inflammation. Since vascular endothelial growth factor (VEGF) is the major architect of vascular remodeling, we sought to examine and elucidate the potential relationship between VEGF and inflammation in the uterine cervix of non-pregnant mice. The animals used were divided into 4 treatment groups: A) negative control (vehicle only), B) positive control (lipopolysaccharide, LPS), C) recombinant VEGF-164 protein, and D) LPS + VEGF blocker (n = 3). After the appropriate treatments, the uterine cervices were harvested and analyzed using real-time PCR and confocal fluorescence microscopy. Results showed that exogenous VEGF upregulates expression of interleukin (IL)-6 and tumor necrosis factor (TNF)-α mRNAs, whereas VEGF blocker partially diminishes the LPS-induced expression of pro-inflammatory factors compared to the positive control group. We conclude that a positive feed-forward relationship likely exists between VEGF and inflammation in the uterine cervix, thus implicating VEGF in inflammation-induced preterm labor.Inflammation is believed to play a role in uterine cervical remodeling and infection-induced preterm labor. During the course of pregnancy, the remodeling uterine cervix is, among other events, characterized by distinct vascular changes, notably, angiogenesis, vasodilation, and vascular permeability (7,(26)(27)(28). Although the functional significance of these changes during uterine cervical remodeling and at birth is, as yet, unclear, we know that vascular remodeling and inflammation are intricately intertwined (4). For instance, three of the five cardinal signs of inflammation are dependent on vascular changes, i.e., redness and heat are dependent on angiogenesis and vasodilation, whereas swelling or edema is dependent on leaky vessels or vascular permeability (33). More importantly, and of relevance to the present study, is the fact that uterine cervical remodeling and the birth process are generally considered inflammatory-like responses (25), in part, due to accumulation of immune cells and expansion of the vascular network in the uterine and uterine cervical tissues. The extent of tissue infiltration by different immune cells varies over the course of pregnancy, during and after birth (4). Data from non-human primate model studies showing successful blockade of infection-induced preterm labor using toll-like receptor 4 antagonists appear to support the role of in-

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“…The key role played by these specific cytokines is shown in mice lacking receptors for both IL-1β and TNF-α, which have significantly lower levels of PGHS-2 mRNA in the myometrium following E. coli administration (Hirsch et al 2006). Aside from the above-mentioned infections, bacterial vaginosis (BV) and STIs are recognised as a risk factor for PTL, although treatment of asymptomatic women with BV does not reduce the rate of preterm births (Romero et al 2001).…”

Section: Figurementioning

confidence: 99%

Myometrial cytokines and their role in the onset of labour

Sivarajasingam

Imami

Johnson

2016

Journal of Endocrinology

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Human labour is an inflammatory event, physiologically driven by an interaction between hormonal and mechanical factors and pathologically associated with infection, bleeding and excessive uterine stretch. The initiation and communicators of inflammation is still not completely understood; however, a key role for cytokines has been implicated. We summarise the current understanding of the nature and role of cytokines, chemokines and hormones and their involvement in signalling within the myometrium particularly during labour.

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Signaling via the type I IL-1 and TNF receptors is necessary for bacterially induced preterm labor in a murine model

Cited by 117 publications

References 41 publications

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

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

Vascular endothelial growth factor induces mRNA expression of pro-inflammatory factors in the uterine cervix of mice

Myometrial cytokines and their role in the onset of labour

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