Expression and Hormonal Regulation of Monocyte Chemotactic Protein-1 in Myometrium and Leiomyomata

Sozen, Ibrahim; Olive, David L.; Arıcı, Aydın

doi:10.1016/s0015-0282(98)00072-7

Cited by 37 publications

(26 citation statements)

References 23 publications

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“…We also found a direct inhibitory effect of P4 on the expression of Ccl-2 gene and immunoreactive Ccl-2 protein in cultured primary myometrial SMCs. These data correspond well with previous findings by Sozen and colleagues (39) reporting that P4 may down-regulate Ccl-2 expression within nonpregnant myometrium. They observed that an absence of sex steroids led to a pronounced elevation of CCL-2 within nonpregnant human myometrium and seemed to inhibit cell proliferation in the tissue while attracting and activating macrophages.…”

Section: Discussionsupporting

confidence: 93%

Monocyte Chemoattractant Protein-1 (CCL-2) Integrates Mechanical and Endocrine Signals That Mediate Term and Preterm Labor

Shynlova

Tsui

Dorogin

et al. 2008

The Journal of Immunology

143

126

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Recent evidence suggests that leukocytes infiltrate uterine tissues at or around the time of parturition, implicating inflammation as a key mechanism of human labor. MCP-1 (also known as C-C chemokine motif ligand 2, CCL-2) is a proinflammatory cytokine that is up-regulated in human myometrium during labor. Myometrium was collected from pregnant rats across gestation and at labor. Total RNA and proteins were subjected to real-time PCR and ELISA, respectively. Ccl-2 gene and protein expression was significantly up-regulated in the gravid rat myometrium before and during labor, which might suggest that it is regulated positively by mechanical stretch of the uterus imposed by the growing fetus and negatively by physiological withdrawal of progesterone (P4). We confirmed in vivo that: 1) administration of P4 receptor antagonist RU486 induced an increase in Ccl-2 mRNA and preterm labor, whereas 2) artificial maintenance of elevated P4 levels at late gestation caused a significant decrease in gene expression and blocked labor; 3) Ccl-2 was elevated specifically in the gravid horn of unilaterally pregnant rats suggesting that mechanical strain imposed by the growing fetus controls its expression in the myometrium; 4) in vitro static mechanical stretch of primary rat myometrial smooth muscle cells (25% elongation) induced a release of Ccl-2 protein, which was repressed by pretreatment with P4 (1 μM); and 5) stretch enhanced their monocyte chemoattractant activity. These data indicate that Ccl-2 protein serves to integrate mechanical and endocrine signals contributing to uterine inflammation and the induction of labor and thus may represent a novel target for therapeutic prevention of preterm labor in humans.

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Section: Discussionsupporting

confidence: 93%

Monocyte Chemoattractant Protein-1 (CCL-2) Integrates Mechanical and Endocrine Signals That Mediate Term and Preterm Labor

Shynlova

Tsui

Dorogin

et al. 2008

The Journal of Immunology

143

126

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“…Even chemokines and their receptors (MIP-1 α , MIP-1 β , RANTES, eotaxin, eotaxin-2, IL-8, CCR1, CCR3, CCR5, CXCR1, and CXCR2 mRNA) have been shown to be mediators of the above mentioned process [118–120]. Sozen et al [121] found that MCP-1 mRNA levels are higher in myometrium compared to leiomyoma and that estrogens and progestins decrease MCP-1 protein production, suggesting that MCP-1 may have antineoplastic activity in leiomyoma. IL-8 and IL-8 receptors type A have been identified with the elevated expression in myometrium compared to leiomyoma [122].…”

Section: Pathogenesis Of Uterine Leiomyomamentioning

confidence: 99%

Uterine Fibroids: Pathogenesis and Interactions with Endometrium and Endomyometrial Junction

Ciavattini

Giuseppe

Stortoni

et al. 2013

Obstetrics and Gynecology International

171

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Uterine leiomyomas (fibroids or myomas) are benign tumors of uterus and clinically apparent in a large part of reproductive aged women. Clinically, they present with a variety of symptoms: excessive menstrual bleeding, dysmenorrhoea and intermenstrual bleeding, chronic pelvic pain, and pressure symptoms such as a sensation of bloatedness, increased urinary frequency, and bowel disturbance. In addition, they may compromise reproductive functions, possibly contributing to subfertility, early pregnancy loss, and later pregnancy complications. Despite the prevalence of this condition, myoma research is underfunded compared to other nonmalignant diseases. To date, several pathogenetic factors such as genetics, microRNA, steroids, growth factors, cytokines, chemokines, and extracellular matrix components have been implicated in the development and growth of leiomyoma. This paper summarizes the available literature regarding the ultimate relative knowledge on pathogenesis of uterine fibroids and their interactions with endometrium and subendometrial myometrium.

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“…Inflammatoryand immune-related cell migration into the inflamed site, as well as local myometrial smooth muscle cells, fibroblasts within the connective tissue, and other vasculatures, all express various types of inflammatory mediators including a large number of cytokines, chemokines, eicosanoids, oxygen and nitrogen radicals, and proteases. 22, [68][69][70][71][72][73] The individual and combined actions of these mediators function to initiate, amplify, and control many molecular events that ultimately lead to resolution of the inflammatory response. At the same time, excess generation of these mediators and prolonged inflammation also serve as plausible mechanisms that initiate cellular transformation of the neighboring cells through DNA damage, leading to the activation of oncogenes and/or inactivation of tumor suppressor genes.…”

Section: Cell Types With Potential Of Myofibroblastic Transformationmentioning

confidence: 99%

Proinflammatory and Profibrotic Mediators: Principal Effectors of Leiomyoma Development as a Fibrotic Disorder

2010

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Leiomyomas are believed to derive from the transformation of myometrial smooth muscle cells/connective tissue fibroblasts. Although the identity of the molecule(s) that initiate such cellular transformation and orchestrate subsequent growth is still unknown, conventional evidence indicates that ovarian steroids are essential for leiomyoma growth. Ovarian steroid action in their target cell/tissue is mediated in part through local expression of various growth factors, cytokines, and chemokines. These autocrine/paracrine molecules with proinflammatory and profibrotic activities serve as major contributing factors in regulating cellular transformation, cell growth and apoptosis, angiogenesis, cellular hypertrophy, and excess tissue turnover, events central to leiomyoma growth. This review addresses the key regulatory functions of proinflammatory and profibrotic mediators and their molecular mechanisms, downstream signaling that regulates cellular events that result in transformation, and commitments of specific cells into forming a cellular environment with a possible role in development and subsequent growth of leiomyomas.

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Expression and Hormonal Regulation of Monocyte Chemotactic Protein-1 in Myometrium and Leiomyomata

Cited by 37 publications

References 23 publications

Monocyte Chemoattractant Protein-1 (CCL-2) Integrates Mechanical and Endocrine Signals That Mediate Term and Preterm Labor

Monocyte Chemoattractant Protein-1 (CCL-2) Integrates Mechanical and Endocrine Signals That Mediate Term and Preterm Labor

Uterine Fibroids: Pathogenesis and Interactions with Endometrium and Endomyometrial Junction

Proinflammatory and Profibrotic Mediators: Principal Effectors of Leiomyoma Development as a Fibrotic Disorder

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