Expression and function of Toll-like receptors in human endometrial epithelial cell lines

Aboussahoud, Wedad; Aflatoonian, Reza; Bruce, Chris; Elliott, Sarah; Ward, Julian; Newton, Sue; Hombach‐Klonisch, Sabine; Klonisch, Thomas; Fazeli, Alireza

doi:10.1016/j.jri.2009.09.008

Cited by 36 publications

(33 citation statements)

References 46 publications

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“…Flagellin has been shown to have diverse immunomodulatory activities which are mostly mediated through the binding with TLR5 expressed on epithelial cells of gastrointestinal tract, macrophages and dendritic cells of hematopoietic origin (40, 41) (42). To explore the mechanism and involvement of flagellin-TLR5 immune interactions in the reduction of GvHD in allogeneic HSCT recipients, we first generated 4 sets of radiation chimeras (B6→KO, KO→B6, B6→B6 and KO→KO described in Materials and Methods).…”

Section: Resultsmentioning

confidence: 99%

“…This finding is unexpected, as activation of host APC through a TLR ligand might be predicted to increase GvHD in allo HSCT recipients(44, 48). Previously published reports by us and others showed that flagellin selectively binds only with TLR5 (49) which is abundantly expressed on cells of various mucosal organs including gastrointestinal tract (GI), lung, uterus, as well as CD11c+CD11b+ hematopoietic cells isolated lamina propria of small intestine, macrophages and dendritic cells (40, 41) (11, 25, 42, 50–52). The effect of flagellin on TLR5-expressing antigen presenting cells (APCs) is primarily to promote a stimulatory immune responses and the generation of inflammatory cytokines in vitro.…”

Section: Discussionmentioning

confidence: 99%

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Flagellin, a TLR5 Agonist, Reduces Graft-versus-Host Disease in Allogeneic Hematopoietic Stem Cell Transplantation Recipients While Enhancing Antiviral Immunity

Hossain

Jaye

Pollack

et al. 2011

The Journal of Immunology

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Graft-versus-host disease (GvHD) is a major cause of morbidity and mortality in patients treated with allogeneic hematopoietic stem cell transplantation (HSCT). Post-transplant immunosuppressive drugs incompletely control GvHD and increase susceptibility to opportunistic infections. In this study we used flagellin, a TLR5 agonist protein (~50 kDa) extracted from bacterial flagella, as a novel experimental treatment strategy to reduce both acute and chronic GvHD in allogeneic HSCT recipient. Based upon the radio-protective effects of flagellin, we hypothesized that flagellin could ameliorate GvHD in lethally irradiated murine models of allogeneic HSCT. Two doses of highly purified flagellin (administered 3 hrs. before irradiation and 24 hrs. after HSCT) reduced GvHD and led to better survival in both H-2b → CB6F1 and H-2k → B6 allogeneic HSCT models while preserving over 99% donor T cells chimerism. Flagellin treatment preserved long-term post-transplant immune reconstitution characterized by more donor thymic-derived CD4+CD25+foxp3+ regulatory T cells (Tregs) and significantly enhanced anti-viral immunity following murine cytomegalovirus (mCMV) infection model. The proliferation index and activation status of donor spleen-derived T cells, and serum concentration of pro-inflammatory cytokines in flagellin-treated recipients were reduced significantly within 4 days post-transplant compared with the PBS-treated control recipients. Allogeneic transplantation of radiation chimeras previously engrafted with TLR5 knockout hematopoietic cells showed that interactions between flagellin and TLR5 expressed on both donor hematopoietic and host non-hematopoietic cells were required to reduce GvHD. Thus, the peri-transplant administration of flagellin is a novel therapeutic approach control GvHD while preserving post-transplant donor immunity.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Flagellin, a TLR5 Agonist, Reduces Graft-versus-Host Disease in Allogeneic Hematopoietic Stem Cell Transplantation Recipients While Enhancing Antiviral Immunity

Hossain

Jaye

Pollack

et al. 2011

The Journal of Immunology

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“…These cytokines modulates systemic and local inflammatory and immune responses (25). Aboussahoud et al demonstrated that TLRs expressed in endometrial epithelial cell lines and their stimulation led to IL-6 and IL-8 production (26). …”

Section: Introductionmentioning

confidence: 99%

TLRs expression in follicular cells of poor ovarian responder

Taghavi

Ashrafi

Karimian

et al. 2012

Journal of Reproductive Immunology

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“…Ishikawa cell line, an endometrial epithelial cell line, previously validated as an in vitro model to study innate immune responses and functions of endometrium [9] was considered to study the host-pathogen interactions. Since genital tuberculosis is characterized by sparse number of bacilli [10], it was of foremost importance to analyze the capacity of this virulent strain to invade and enter the endometrial epithelial cell.…”

Section: Virulent M Tuberculosis Is Internalized During Infection Inmentioning

confidence: 99%

Modulation of host ubiquitin system genes in human endometrial cell line infected with Mycobacterium tuberculosis

Meenu

Thiagarajan

Ramalingam

et al. 2015

Med Microbiol Immunol

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Endometrium is one of the most commonly affected sites in genital tuberculosis. The understanding of its interaction with the tubercle bacilli is of paramount importance for studying the pathogenesis of this disease. The main objective of this work was to study the interplay between Mycobacterium tuberculosis and host endometrial epithelial cell lines (Ishikawa cell lines), and to identify the differentially expressed genes upon tuberculosis infection. To study this, suppression subtractive hybridization library was constructed using M. tuberculosis H37Rv-infected Ishikawa cell line harvested 24 h post-infection. The subtracted cDNA library was screened, and 105 differentially expressed genes were identified and grouped based on their functions. Since ubiquitination process has gained importance in targeting M. tuberculosis to xenophagy, ubiquitin system genes obtained in the library were selected, and time course analysis of their gene expression was performed. We observed an upregulation of mkrn1 and cops5 and downregulation of zfp91, ndfip2, ube2f, rnft1, psmb6, and psmd13 at 24 h post-infection. From the results obtained, we surmise that ubiquitination pathway genes may have roles in combating tuberculosis which are yet uncharted.

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Expression and function of Toll-like receptors in human endometrial epithelial cell lines

Cited by 36 publications

References 46 publications

Flagellin, a TLR5 Agonist, Reduces Graft-versus-Host Disease in Allogeneic Hematopoietic Stem Cell Transplantation Recipients While Enhancing Antiviral Immunity

Flagellin, a TLR5 Agonist, Reduces Graft-versus-Host Disease in Allogeneic Hematopoietic Stem Cell Transplantation Recipients While Enhancing Antiviral Immunity

TLRs expression in follicular cells of poor ovarian responder

Modulation of host ubiquitin system genes in human endometrial cell line infected with Mycobacterium tuberculosis

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