Expression of Toll‐like Receptors in Human Endometrial Epithelial Cells and Cell Lines

Young, Steven L.; Lyddon, Terri D.; Jorgenson, Rebecca L.; Misfeldt, Michael L.

doi:10.1111/j.1600-0897.2004.00189.x

Cited by 89 publications

(91 citation statements)

References 31 publications

(35 reference statements)

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“…Fichorova et al [21] demonstrated cervicovaginal epithelial cell line expression of TLR3. Our group established that endometrial epithelial tissues and cell lines express TLR3 as well as other TLRs [22]. Schaefer et al [23] independently confirmed this observation.…”

Section: Introductionsupporting

confidence: 69%

Human Endometrial Epithelial Cells Cyclically Express Toll-Like Receptor 3 (TLR3) and Exhibit TLR3-Dependent Responses to dsRNA

et al. 2005

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Toll-like receptor 3 (TLR3) responds to dsRNA, a product of most viral life cycles, and initiates production of proinflammatory and antiviral cytokines. The role of TLR3 in human mucosal immunity of the endometrium has not been examined. The effects of TLR3 ligation in endometrial epithelium could be significant as the endometrium is a significant site for viral entry and infection. Additionally, the cytokine milieu plays an essential role in normal functions of the endometrium such as uterine cycle progression, epithelial proliferation and shedding, and embryo implantation. In this study, we demonstrated cycle dependent expression of functional TLR3 in primary endometrial epithelial tissue and expression of intracellular TLR3 in human endometrial epithelial cell lines. We established that stimulation of TLR3-positive cell lines and primary human endometrial epithelial cells with dsRNA leads to TLR3-dependent expression of interleukin (IL)-6, IL-8, interferon (IFN)-inducible protein 10, RANTES, and IFN-β. These results indicate that the cytokine profile of human endometrial epithelial cells can be modified through TLR3 stimulation. Our findings suggest that TLR3 is involved in the immune responses of endometrial epithelial cells after exposure to dsRNA and has the potential to alter the cytokine milieu and influence the outcome and consequences of infection.

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Section: Introductionsupporting

confidence: 69%

Human Endometrial Epithelial Cells Cyclically Express Toll-Like Receptor 3 (TLR3) and Exhibit TLR3-Dependent Responses to dsRNA

et al. 2005

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“…In order to understand the expression patterns of the 20q defensin genes in female reproductive tissues, endometrial samples were obtained under a protocol approved by the UNC School of Medicine IRB from Dr Bruce Lessey (Greenville Hospital, Greenville, SC, USA) as described. 42 In all, 2 mg of total RNA was reverse transcribed using 50 U Stratascriptt (Stratagene, La Jolla, CA, USA) according to the supplier's instructions with 0.5 mg of oligodT (Invitrogen). Gene-specific intron spanning primer sequences for b-defensin DEFB118-DEFB123 and peptidyl isomerase (PPIA) were as follows:…”

Section: Methodsmentioning

confidence: 99%

Identification, characterization, and evolution of a primate β-defensin gene cluster

et al. 2005

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Defensins are members of a large diverse family of cationic antimicrobial peptides that share a signature pattern consisting of six conserved cysteine residues. Defensins have a wide variety of functions and their disruption has been implicated in various human diseases. Here we report the characterization of DEFB119-DEFB123, five genes in the human b-defensin cluster locus on chromosome 20q11.1. The genomic structures of DEFB121 and DEFB122 were determined in silico. Sequences of the five macaque orthologs were obtained and expression patterns of the genes were analyzed in humans and macaque by semiquantitative reverse transcription polymerase chain reaction. Expression was restricted to the male reproductive tract. The genes in this cluster are differentially regulated by androgens. Evolutionary analyses suggest that this cluster originated by a series of duplication events and by positive selection. The evolutionary forces driving the proliferation and diversification of these defensins may be related to reproductive specialization and/or the host-parasite coevolutionary process.

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“…The increase in expression of TLR2, TLR7, TLR8, and TLR9 in the endometrium during early pregnancy probably results from both progesterone-dependent recruitment of immune cells enriched in these particular TLRs (Segerson et al 1991, Plaks et al 2008, Gomez-Lopez et al 2010, Mansouri-Attia et al 2012 and changes in uterine gene expression required for pregnancy (Young et al 2004, Jorgenson et al 2005, Aflatoonian et al 2007, Hirata et al 2007, Turner et al 2012. In view of the significant increase in steady-state levels of both TLR7 and TLR8 mRNAs in uteri of early pregnant ewes, we determined cell-specific expression of TLR7 and TLR8 proteins to be particularly abundant in uterine LE and sGE and expressed in a temporal and cell-specific manner that differed due to reproductive TLR and establishment of pregnancy in sheep status, which supports results obtained from previous studies (Jorgenson et al 2005, Aflatoonian et al 2007, Hirata et al 2007.…”

Section: Discussionmentioning

confidence: 99%

“…The finding of TLRs in non-typical immune cells such as the epithelia (Young et al 2004, Turner et al 2012 has implicated these receptors in many physiological events besides pathogen recognition (Li et al 2010). Available evidence indicates potential involvement of TLRs in mammalian reproduction, which requires an appropriate inflammatory balance among steroid hormones, cytokines, and prostaglandins to assure cyclical uterine remodeling for establishment and maintenance of pregnancy (King & Critchley 2010, Ott & Gifford 2010, Dorniak et al 2011.…”

Section: Introductionmentioning

confidence: 99%

Involvement of TLR7 and TLR8 in conceptus development and establishment of pregnancy in sheep

Ruiz-Gonzalez¹,

Minten²,

Wang³

et al. 2015

Reproduction

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Toll-like receptors (TLRs) belong to the innate immune system and regulate inflammatory events that affect mammalian reproduction.In Study 1, we demonstrated that abundance of ovine TLR1-TLR9 mRNAs in the uterus differs due to reproductive status (TLR2, TLR3, TLR7, and TLR8) and the day of the estrous cycle and pregnancy (TLR1-TLR3, TLR5-TLR7, and TLR9). Expression of TLR7 and TLR8 proteins was localized primarily to uterine epithelia and stroma and regulated in a temporal manner. In Study 2, we determined that ovine conceptuses express TLR7 and TLR8 on all days studied and that expression of the envelope protein of ovine endogenous retrovirus (enJSRV-Env) declined in conceptus trophectoderm from Day 13 to Day 16 of pregnancy. In Study 3, loss-of-function experiments were conducted in vivo using morpholino antisense oligonucleotides (MAOs) injected into the uterine lumen to block synthesis of TLR7 and TLR8 proteins, individually and jointly. Conceptuses were recovered on Day 16 to assess their morphology. MAO-treated conceptuses were developmentally retarded, produced less interferon tau (IFNT), and had fewer binucleate cells (BNCs) compared with MAO-Controls. Moreover, expression of enJSRV-Env mRNA in MAO-TLR7 conceptuses was greater than that for MAO-Control and MAO-TLR8 conceptuses, but similar to MAO-TLR7/TLR8 conceptuses. Results of this study indicated differences in TLR1-TLR9 expression due to reproductive status and the day of the estrous cycle and pregnancy. TLR7 and TLR8 also influence development, enJSRV-Env abundance, secretion of IFNT, and formation of BNCs by conceptuses. These findings corroborate our hypothesis that TLR7 and TLR8 mediate pathways whereby enJSRV-Env regulates key peri-implantation events in conceptus development and differentiated functions of trophectoderm cells.

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Expression of Toll‐like Receptors in Human Endometrial Epithelial Cells and Cell Lines

Cited by 89 publications

References 31 publications

Human Endometrial Epithelial Cells Cyclically Express Toll-Like Receptor 3 (TLR3) and Exhibit TLR3-Dependent Responses to dsRNA

Human Endometrial Epithelial Cells Cyclically Express Toll-Like Receptor 3 (TLR3) and Exhibit TLR3-Dependent Responses to dsRNA

Identification, characterization, and evolution of a primate β-defensin gene cluster

Involvement of TLR7 and TLR8 in conceptus development and establishment of pregnancy in sheep

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