scholarly journals Infection of Mast Cells with Live Streptococci Causes a Toll-Like Receptor 2- and Cell-Cell Contact-Dependent Cytokine and Chemokine Response

2009 ◽  
Vol 78 (2) ◽  
pp. 854-864 ◽  
Author(s):  
Elin Rönnberg ◽  
Bengt Guss ◽  
Gunnar Pejler
Keyword(s):  
Mast Cells ◽  
Bacterial Infection ◽  
Molecular Mechanisms ◽  
Interleukin 4 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cell Contact ◽  
Toll Like Receptor ◽  
Gram Positive ◽  
Toll Like Receptor 2 ◽  
Cell Cell

ABSTRACT Mast cells (MCs) are strongly implicated in immunity toward bacterial infection, but the molecular mechanisms by which MCs contribute to the host response are only partially understood. We addressed this issue by examining the direct effects of a Gram-positive pathogen, Streptococcus equi, on bone marrow-derived MCs (BMMCs). Ultrastructural analysis revealed extensive formation of dilated rough endoplasmic reticulum in response to bacterial infection, indicating strong induction of protein synthesis. However, the BMMCs did not show signs of extensive degranulation, and this was supported by only slow release of histamine in response to infection. Coculture of live bacteria with BMMCs caused a profound secretion of CCL2/MCP-1, CCL7/MCP-3, CXCL2/MIP-2, CCL5/RANTES, interleukin-4 (IL-4), IL-6, IL-12, IL-13, and tumor necrosis factor alpha, as shown by antibody-based cytokine/chemokine arrays and/or enzyme-linked immunosorbent assay. In contrast, heat-inactivated bacteria caused only minimal cytokine/chemokine release. The cytokine/chemokine responses were substantially attenuated in Toll-like receptor 2-deficient BMMCs and were strongly dependent on cell-cell contacts between bacteria and BMMCs. Gene chip microarray analysis confirmed a massively upregulated expression of the genes coding for the secreted cytokines and chemokines and also identified a pronounced upregulation of numerous additional genes, including transcription factors, signaling molecules, and proteases. Together, the present study outlines MC-dependent molecular events associated with Gram-positive infection and thus provides an advancement in our understanding of how MCs may contribute to host defense toward bacterial insults.

scholarly journals Interleukin-6 via Toll-Like Receptor 3 Signaling Attenuates the Expression of Proinflammatory Chemokines in Human Podocytes

2021 ◽  
Vol 46 (2) ◽  
pp. 207-218
Author(s):  
Hidenori Umetsu ◽  
Shojiro Watanabe ◽  
Tadaatsu Imaizumi ◽  
Tomomi Aizawa ◽  
Koji Tsugawa ◽  
...  
Keyword(s):  
Rna Interference ◽  
Molecular Mechanisms ◽  
Kidney Diseases ◽  
Enzyme Linked Immunosorbent Assay ◽  
Toll Like Receptor ◽  
Induced Expression ◽  
Inflammatory Reactions ◽  
Monocyte Chemoattractant Protein 1 ◽  
Polycytidylic Acid ◽  
Tlr3 Signaling

<b><i>Background:</i></b> Although toll-like receptor 3 (TLR3) signaling is involved in the development of certain chronic kidney diseases, the specific molecular mechanisms underlying inflammatory reactions via activation of TLR3 signaling in human podocytes remain unclear. Interleukin (IL)-6 is a pleiotropic cytokine associated with innate and adaptive immune responses; however, little is known about the implication of IL-6 via the activation of regional TLR3 signaling in the inflammatory reactions in human podocytes. <b><i>Methods:</i></b> We treated immortalized human podocytes with polyinosinic-polycytidylic acid (poly IC), an authentic viral double-stranded RNA, and assessed the expression of IL-6, monocyte chemoattractant protein-1 (MCP-1), and C-C motif chemokine ligand 5 (CCL5) using quantitative real-time reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. To further elucidate the poly IC-induced signaling pathway, we subjected the cells to RNA interference against IFN-β and IL-6. <b><i>Results:</i></b> We found that the activation of TLR3 induced expression of IL-6, MCP-1, CCL5, and IFN-β in human podocytes. RNA interference experiments revealed that IFN-β was involved in the poly IC-induced expression of IL-6, MCP-1, and CCL5. Interestingly, IL-6 knockdown markedly increased the poly IC-induced expression of MCP-1 and CCL5. Further, treatment of cells with IL-6 attenuated the expression of CCL5 and MCP-1 mRNA and proteins. <b><i>Conclusion:</i></b> IL-6 induced by TLR3 signaling negatively regulates the expression of representative TLR3 signaling-dependent proinflammatory chemokines in human podocytes.

Toll-like receptor 2, 3, 4, 5 ligands and interleukin-4 synergistically induce TARC production in nasal polyp fibroblasts

2008 ◽  
Vol 35 (4) ◽  
pp. 515-520 ◽  
Author(s):  
Manabu Nonaka ◽  
Nozomu Ogihara ◽  
Akira Fukumoto ◽  
Atsuko Sakanushi ◽  
Ruby Pawankar ◽  
...  
Keyword(s):  
Nasal Polyp ◽  
Interleukin 4 ◽  
Toll Like Receptor ◽  
Toll Like Receptor 2

scholarly journals Regulation of myosin activation during cell–cell contact formation by Par3-Lgl antagonism: entosis without matrix detachment

2012 ◽  
Vol 23 (11) ◽  
pp. 2076-2091 ◽  
Author(s):  
Qingwen Wan ◽  
Jing Liu ◽  
Zhen Zheng ◽  
Huabin Zhu ◽  
Xiaogang Chu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Molecular Mechanisms ◽  
Myosin Ii ◽  
Coiled Coil ◽  
Host Cells ◽  
Cell Contact ◽  
Contact Formation ◽  
Cell Internalization ◽  
Mammary Gland Epithelial Cells ◽  
Cell Cell

Cell–cell contact formation following cadherin engagement requires actomyosin contraction along the periphery of cell–cell contact. The molecular mechanisms that regulate myosin activation during this process are not clear. In this paper, we show that two polarity proteins, partitioning defective 3 homologue (Par3) and mammalian homologues of Drosophila Lethal (2) Giant Larvae (Lgl1/2), antagonize each other in modulating myosin II activation during cell–cell contact formation in Madin-Darby canine kidney cells. While overexpression of Lgl1/2 or depletion of endogenous Par3 leads to enhanced myosin II activation, knockdown of Lgl1/2 does the opposite. Intriguingly, altering the counteraction between Par3 and Lgl1/2 induces cell–cell internalization during early cell–cell contact formation, which involves active invasion of the lateral cell–cell contact underneath the apical-junctional complexes and requires activation of the Rho–Rho-associated, coiled-coil containing protein kinase (ROCK)–myosin pathway. This is followed by predominantly nonapoptotic cell-in-cell death of the internalized cells and frequent aneuploidy of the host cells. Such effects are reminiscent of entosis, a recently described process observed when mammary gland epithelial cells were cultured in suspension. We propose that entosis could occur without matrix detachment and that overactivation of myosin or unbalanced myosin activation between contacting cells may be the driving force for entosis in epithelial cells.

scholarly journals Toll-like receptor 2 (TLR2) and TLR4 differentially activate human mast cells

2003 ◽  
Vol 33 (4) ◽  
pp. 899-906 ◽  
Author(s):  
Sonia Varadaradjalou ◽  
Frédéric Féger ◽  
Nathalie Thieblemont ◽  
Nadine Ben Hamouda ◽  
Jean-Marie Pleau ◽  
...  
Keyword(s):  
Mast Cells ◽  
Toll Like Receptor ◽  
Human Mast Cells ◽  
Toll Like Receptor 2

scholarly journals Polarity and epithelial-mesenchymal transition of retinal pigment epithelial cells in proliferative vitreoretinopathy

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10136
Author(s):  
Hui Zou ◽  
Chenli Shan ◽  
Linlin Ma ◽  
Jia Liu ◽  
Ning Yang ◽  
...  
Keyword(s):  
Proliferative Vitreoretinopathy ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Retinal Pigment ◽  
Notch Pathway ◽  
Retinal Pigment Epithelial Cells ◽  
Cell Contact ◽  
Mesenchymal Transition ◽  
Rpe Cells ◽  
Cell Cell

Under physiological conditions, retinal pigment epithelium (RPE) is a cellular monolayer composed of mitotically quiescent cells. Tight junctions and adherens junctions maintain the polarity of RPE cells, and are required for cellular functions. In proliferative vitreoretinopathy (PVR), upon retinal tear, RPE cells lose cell-cell contact, undergo epithelial-mesenchymal transition (EMT), and ultimately transform into myofibroblasts, leading to the formation of fibrocellular membranes on both surfaces of the detached retina and on the posterior hyaloids, which causes tractional retinal detachment. In PVR, RPE cells are crucial contributors, and multiple signaling pathways, including the SMAD-dependent pathway, Rho pathway, MAPK pathways, Jagged/Notch pathway, and the Wnt/β-catenin pathway are activated. These pathways mediate the EMT of RPE cells, which play a key role in the pathogenesis of PVR. This review summarizes the current body of knowledge on the polarized phenotype of RPE, the role of cell-cell contact, and the molecular mechanisms underlying the RPE EMT in PVR, emphasizing key insights into potential approaches to prevent PVR.

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