Polarized Epithelial Cells Secrete Interleukin 6 Apically in the Bovine Endometrium1

Healy, Laura L.; Cronin, James G.; Sheldon, I. Martin

doi:10.1095/biolreprod.115.127936

Cited by 30 publications

(32 citation statements)

References 56 publications

(121 reference statements)

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“…The induction of inflammatory cytokine mRNA in response to LPS stimulation confirms that isolated and cultured endometrial cells retain the ability to respond to bacterial stimuli in-vitro. While the induction of the cytokines IL8 and IL6 by endometrial cells has been previously reported (Cronin et al 2012;Healy et al 2015), their induction here, in addition to the antimicrobial S100A8 and S100A9, confirms that our improved protocol for isolating and culturing endometrial cells provides a practical option for the study of bovine inflammatory responses in-vitro. This model will facilitate investigations into the production of immune molecules such as cytokines, chemokines, HDPs and acute phase proteins under defined inflammatory conditions.…”

Section: Discussionsupporting

confidence: 82%

Improved filtration method to isolate pure populations of primary bovine endometrial epithelial and stromal cells for immunological studies

et al. 2020

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Objectives Isolation and culture of distinct primary endometrial cells are key to reliable in-vitro models to investigate the uterine immune response and optimse new disease interventions. Details on the isolation method and purity of distinct cell populations is lacking in currently available protocols leading to inconsistent results across laboratories. Methods Bovine endometrial tissue from non-pregnant bovine uteri were collected immediately post-mortem and separated using differential size filtering. Isolations (n = 15) yielded an average of 3.1 × 10 5 ± 0.7 × 10 5 epithelial cells and 1.88 × 10 6 ± 5.44 × 10 5 stromal fibroblasts per uterine horn. Following expansion in culture, the purity of cell populations was confirmed using morphology and positive staining for cytokeratin and vimentin which identifies epithelial and stromal fibroblast populations, respectively. Using PCR, cDNA from both cell populations was negative for CD45, a marker of immune cells. Results On challenge with a bacterial PAMP (LPS), epithelial and stromal fibroblasts showed a marked increase in the expression of the inflammatory mediators IL8, IL6, S100A8 and S100A9, with both cell populations displaying distinct expression profiles. Here we provide a detailed methodology on the culture of primary bovine endometrial epithelial and stromal cells and demonstrate these cells provide a physiologically relevant model for studies of endometrial inflammation and its regulation.

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Section: Discussionsupporting

confidence: 82%

Improved filtration method to isolate pure populations of primary bovine endometrial epithelial and stromal cells for immunological studies

et al. 2020

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“…Similar to reports in mammalian epithelial cells [30,31], Drosophila Upd is secreted from the apical surface of epithelial cells to transduce the signal to the neighboring cells, where it binds the receptor Domeless, which is also localized on the apical membrane [32]. Therefore, apical delamination in the valley-folded hotspot where the JAK/STAT ligand abundantly accumulates favors the survival and proliferation of the pro-tumor cells.…”

Section: Resultsmentioning

confidence: 59%

Epithelial Tumors Originate in Tumor Hotspots, a Tissue-Intrinsic Microenvironment

2016

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Malignant tumors are caused by uncontrolled proliferation of transformed mutant cells that have lost the ability to maintain tissue integrity. Although a number of causative genetic backgrounds for tumor development have been discovered, the initial steps mutant cells take to escape tissue integrity and trigger tumorigenesis remain elusive. Here, we show through analysis of conserved neoplastic tumor-suppressor genes (nTSGs) in Drosophila wing imaginal disc epithelia that tumor initiation depends on tissue-intrinsic local cytoarchitectures, causing tumors to consistently originate in a specific region of the tissue. In this “tumor hotspot” where cells constitute a network of robust structures on their basal side, nTSG-deficient cells delaminate from the apical side of the epithelium and begin tumorigenic overgrowth by exploiting endogenous Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling activity. Conversely, in other regions, the “tumor coldspot” nTSG-deficient cells are extruded toward the basal side and undergo apoptosis. When the direction of delamination is reversed through suppression of RhoGEF2, an activator of the Rho family small GTPases, and JAK/STAT is activated ectopically in these coldspot nTSG-deficient cells, tumorigenesis is induced. These data indicate that two independent processes, apical delamination and JAK/STAT activation, are concurrently required for the initiation of nTSG-deficient-induced tumorigenesis. Given the conservation of the epithelial cytoarchitecture, tumorigenesis may be generally initiated from tumor hotspots by a similar mechanism.

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“…These results indicate that nTSG-knockdown cells exploit local endogenous activity of the JAK/STAT pathway to survive and proliferate [9] (Figure 4). Similar to reports in mammalian epithelial cells [55,56], Drosophila Upd is secreted from the apical surface of epithelial cells to transduce the signal to the neighboring cells, where it binds the receptor Domeless, which is also localized on the apical membrane [57]. Therefore, apical delamination in the valley-folded hotspot where the proinflammatory JAK/STAT ligand abundantly accumulates provides the pro-tumor cells with a crucial survival advantage.…”

Section: Endogenous Oncogenic Signaling and Survival Of Delaminated Cmentioning

confidence: 63%

Tissue-Intrinsic Tumor Hotspots: Terroir for Tumorigenesis

Tamori

Deng

2017

Trends in Cancer

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Epithelial tissues are highly organized systems with a remarkable homeostatic ability to maintain morphology through regulation of cellular proliferation and tissue integrity. This robust self-organizing system is progressively disrupted during tumor development. Recent studies of conserved tumor-suppressor genes in Drosophila showed how pro-tumor cells deviate from the robustly organized tissue microenvironment to take the first steps into becoming aggressive tumors. Here we review the ‘tumor hotspot’ hypothesis that explains how the tissue-intrinsic local microenvironment has a pivotal role in the initial stage of tumorigenesis in Drosophila epithelia and discuss comparable mechanisms in mammalian tissues.

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Polarized Epithelial Cells Secrete Interleukin 6 Apically in the Bovine Endometrium1

Cited by 30 publications

References 56 publications

Improved filtration method to isolate pure populations of primary bovine endometrial epithelial and stromal cells for immunological studies

Improved filtration method to isolate pure populations of primary bovine endometrial epithelial and stromal cells for immunological studies

Epithelial Tumors Originate in Tumor Hotspots, a Tissue-Intrinsic Microenvironment

Tissue-Intrinsic Tumor Hotspots: Terroir for Tumorigenesis

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