Astrocyte-shed extracellular vesicles regulate the peripheral leukocyte response to inflammatory brain lesions
| العنوان: | Astrocyte-shed extracellular vesicles regulate the peripheral leukocyte response to inflammatory brain lesions |
|---|---|
| المؤلفون: | Bezawit W. Megra, Kennith W. Witwer, Daniel C. Anthony, Dionna W. Williams, Nino Tabatadze, Joan W. Berman, Patrizia Casaccia, Luis B. Tovar-y-Romo, Marlene Kanmogne, Mihyun Bae, Amanda L. Trout, Seung Wan Yoo, Norman J. Haughey, Robert N. Cole, Alex M. Dickens, Mar Gacias |
| المصدر: | Science Signaling. 10 |
| بيانات النشر: | American Association for the Advancement of Science (AAAS), 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Pathology, medicine.medical_specialty, Blotting, Western, Interleukin-1beta, Mice, Transgenic, Inflammation, Ceramides, Biochemistry, Extracellular Vesicles, 03 medical and health sciences, 0302 clinical medicine, Immune system, Transcellular Cell Migration, RNA interference, microRNA, medicine, Animals, Secretion, Molecular Biology, Cells, Cultured, Mice, Knockout, business.industry, Brain, Cell Biology, medicine.disease, Mice, Inbred C57BL, Blot, Microscopy, Electron, Sphingomyelin Phosphodiesterase, 030104 developmental biology, medicine.anatomical_structure, Animals, Newborn, Microscopy, Fluorescence, Astrocytes, Immunology, Leukocytes, Mononuclear, Cytokines, RNA Interference, Inflammation Mediators, medicine.symptom, business, Infiltration (medical), 030217 neurology & neurosurgery, Astrocyte |
| الوصف: | Brain injury induces a peripheral acute cytokine response that directs the transmigration of leukocytes into the brain. Because this brain-to-peripheral immune communication affects patient recovery, understanding its regulation is important. Using a mouse model of inflammatory brain injury, we set out to find a soluble mediator for this phenomenon. We found that extracellular vesicles (EVs) shed from astrocytes in response to intracerebral injection of interleukin-1β (IL-1β) rapidly entered into peripheral circulation and promoted the transmigration of leukocytes through modulation of the peripheral acute cytokine response. Bioinformatic analysis of the protein and microRNA cargo of EVs identified peroxisome proliferator–activated receptor α (PPARα) as a primary molecular target of astrocyte-shed EVs. We confirmed in mice that astrocytic EVs promoted the transmigration of leukocytes into the brain by inhibiting PPARα, resulting in the increase of nuclear factor κB (NF-κB) activity that triggered the production of cytokines in liver. These findings expand our understanding of the mechanisms regulating communication between the brain and peripheral immune system and identify astrocytic EVs as a molecular regulator of the immunological response to inflammatory brain damage. |
| تدمد: | 1937-9145 1945-0877 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::10abd14a0292928187ea2d69ac6bbba3Test https://doi.org/10.1126/scisignal.aai7696Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....10abd14a0292928187ea2d69ac6bbba3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19379145 19450877 |
|---|