Proinflammatory role of epithelial cell–derived exosomes in allergic airway inflammation

Kulshreshtha, Ankur; Ahmad, Tanveer; Agrawal, Anurag; Ghosh, Balaram

doi:10.1016/j.jaci.2012.12.1565

Cited by 239 publications

(255 citation statements)

References 51 publications

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“…Indeed, they found that systemically administration of GW4869 could reduce the total exosomes in serum and treat allergic, cardiac and Alzheimer's dysfunction 29, 30, 31. Thus, our findings provide a potential method to prevent endothelial inflammation and atherosclerosis.…”

Section: Discussionmentioning

confidence: 63%

Exosomes derived from mature dendritic cells increase endothelial inflammation and atherosclerosis via membrane TNF‐α mediated NF‐κB pathway

Gao

Yuan

et al. 2016

J Cellular Molecular Medi

223

155

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Whether dendritic cell (DC) derived exosomes play a role in the progression of endothelial inflammation and atherosclerosis remains unclear. Using a transwell system and exosome release inhibitor GW4869, we demonstrated that mature DCs contributed to endothelial inflammation and exosomes were involved in the process. To further confirm this finding, we isolated exosomes from bone marrow dendritic cell (BMDC) culture medium (named DC‐exos) and stimulated human umbilical vein endothelial cell (HUVEC) with these DC‐exos. We observed that mature DC‐exos increased HUVEC inflammation through NF‐κB pathway in a manner similar to that of lipopolysaccharide. After a protein array analysis of exosomes, we identified and confirmed tumour necrosis factor (TNF)‐α on exosome membrane being the trigger of NF‐κB pathway in HUVECs. We then performed an in vivo study and found that the aorta endothelial of mice could uptake intravenously injected exosomes and was activated by these exosomes. After a period of 12 weeks of mature DC‐exos injection into ApoE−/− mice, the atherosclerotic lesions significantly increased. Our study demonstrates that mature DCs derived exosomes increase endothelial inflammation and atherosclerosis via membrane TNF‐α mediated NF‐κB pathway. This finding extends our knowledge on how DCs affect inflammation and provides a potential method to prevent endothelial inflammation and atherosclerosis.

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Section: Discussionmentioning

confidence: 63%

Exosomes derived from mature dendritic cells increase endothelial inflammation and atherosclerosis via membrane TNF‐α mediated NF‐κB pathway

Gao

Yuan

et al. 2016

J Cellular Molecular Medi

223

155

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“…7 Extracellular vesicles represent a new component of this supportive microenvironment, are released by malignant cells and play an important role in cancer cell communication with their environment. [8][9][10][11] Exosomes are small vesicles (50-150 nm) generated via an endocytic pathway and are expressing chaperones (HSP70, HSP90) and tetraspanins (CD9, CD63, CD81). Exosomes contain proteins, DNA, noncoding RNAs, and mRNAs, and specific sorting mechanisms were proposed for loading selected molecules into exosomes.…”

Section: Introductionmentioning

confidence: 99%

Exosomes released by chronic lymphocytic leukemia cells induce the transition of stromal cells into cancer-associated fibroblasts

Paggetti

Haderk

Seiffert

et al. 2015

Blood

400

397

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Luxembourg Key Points• CLL-derived exosomes are internalized by stromal cells, deliver functional microRNA and proteins, and activate key signaling pathways.• Stromal cells exposed to CLLderived exosomes demonstrate a CAF-like phenotype and secrete factors promoting CLL cell survival.Exosomes derived from solid tumor cells are involved in immune suppression, angiogenesis, and metastasis, but the role of leukemia-derived exosomes has been less investigated. The pathogenesis of chronic lymphocytic leukemia (CLL) is stringently associated with a tumorsupportive microenvironment and a dysfunctional immune system. Here, we explore the role of CLL-derived exosomes in the cellular and molecular mechanisms by which malignant cells create this favorable surrounding. We show that CLL-derived exosomes are actively incorporated by endothelial and mesenchymal stem cells ex vivo and in vivo and that the transfer of exosomal protein and microRNA induces an inflammatory phenotype in the target cells, which resembles the phenotype of cancer-associated fibroblasts (CAFs). As a result, stromal cells show enhanced proliferation, migration, and secretion of inflammatory cytokines, contributing to a tumor-supportive microenvironment. Exosome uptake by endothelial cells increased angiogenesis ex vivo and in vivo, and coinjection of CLL-derived exosomes and CLL cells promoted tumor growth in immunodeficient mice. Finally, we detected a-smooth actin-positive stromal cells in lymph nodes of CLL patients. These findings demonstrate that CLL-derived exosomes actively promote disease progression by modulating several functions of surrounding stromal cells that acquire features of cancer-associated fibroblasts. (Blood. 2015;126(9):1106-1117

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“…[27][28][29] Recently, exosome secretion was shown to enhance chemotaxis of neutrophils and macrophages. 21,30,31 However, the role of exosome secretion in cancer cell chemotaxis is unknown.…”

Section: Introductionmentioning

confidence: 99%

Exosome secretion promotes chemotaxis of cancer cells

Sung

Weaver

2017

Cell Adhesion & Migration

105

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Migration of cells toward chemical cues, or chemotaxis, is important for many biologic processes such as immune defense, wound healing and cancer metastasis. Although chemotaxis is thought to occur in cancer cells, it is less well characterized than chemotaxis of professional immune cells such as neutrophils. Here, we show that cancer cell chemotaxis relies on secretion of exosome-type extracellular vesicles. Migration of fibrosarcoma cells toward a gradient of exosome-depleted serum was diminished by knockdown of the exosome secretion regulator Rab27a. Rescue experiments in which chemotaxis chambers were coated with purified extracellular vesicles demonstrate that exosomes but not microvesicles affect both speed and directionality of migrating cells. Chamber coating with purified fibronectin and fibronectin-depleted exosomes demonstrates that the exosome cargo fibronectin promotes cell speed but cannot account for the role of exosomes in promoting directionality of fibrosarcoma cell movement during chemotaxis. These experiments indicate that exosomes contain multiple motility-promoting cargoes that contribute to different aspects of cell motility.

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Proinflammatory role of epithelial cell–derived exosomes in allergic airway inflammation

Cited by 239 publications

References 51 publications

Exosomes derived from mature dendritic cells increase endothelial inflammation and atherosclerosis via membrane TNF‐α mediated NF‐κB pathway

Exosomes derived from mature dendritic cells increase endothelial inflammation and atherosclerosis via membrane TNF‐α mediated NF‐κB pathway

Exosomes released by chronic lymphocytic leukemia cells induce the transition of stromal cells into cancer-associated fibroblasts

Exosome secretion promotes chemotaxis of cancer cells

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