التفاصيل البيبلوغرافية
| العنوان: |
Inflammasome activation in human and mouse macrophages engulfing autophagic dying cells ; Inflammasome Activation in Human and Mouse Macrophages Engulfing Autophagic Dying Cells |
| المؤلفون: |
Ayna, Gizem |
| المساهمون: |
Fésüs, László, Ayna, Gizem, Molekuláris sejt- és immunbiológia doktori iskola, DE--OEC--Általános Orvostudományi Kar -- |
| سنة النشر: |
2012 |
| المجموعة: |
University of Debrecen Electronic Archive (DEA) / Debreceni Egyetem elektronikus Archívum |
| مصطلحات موضوعية: |
Ba/F3, MCF-7, autophagic cell death, phagocytosis, macrophages, NALP-3, inflammasome activation, IL-1β secretion, ATP, P2X7, pannexin-1 channel, Elméleti orvostudományok, Orvostudományok |
| الوصف: |
Phagocytosis of PAMPs, DAMPs and certain dying cells can activate the inflammasome pathway in macrophages. In our study, we show that both human and mouse macrophages display a pro-inflammatory response to autophagic dying MCF-7 and Ba/F3 cells, but not to living, apoptotic, necrotic or necrostatin-1 treated ones. When we investigated this phenomenon, further it was found that caspase-1 was activated and IL-1β was processed and then secreted in a MyD88-independent manner. Neither caspase-1 inhibited nor caspase-1 deficient macrophages could trigger IL-1β release due to the lack of key component for pro-IL-1β cleavage and maturation before its secretion. Next we clarified which inflammasome is activated by autophagic dying cells and found that NALP-3 deficient macrophages displayed reduced IL-1β secretion, which was also observed in macrophages in which the NALP-3 gene was knocked down. Next, we investigated the upstream mechanism of NALP-3 inflammasome activation triggered by autophagic dying cells. Our results show that during phagocytosis of autophagic dying MCF-7 and Ba/F3 cells exogenous ATP is acting through P2X7 receptor, initiates K+ efflux, inflammasome activation and secretion of IL-1β from human and mouse macrophages. Calreticulin exposure on autophagic dying MCF-7 cells do not play role in inflammasome activation. ATP was secreted from human macrophages during co-incubation with autophagic dying MCF-7 cells which did not release ATP. However, autophagic dying Ba/F3 cells were the source the ATP which activated the P2X7 receptor and lead to inflammasome activation in mouse macrophages. We further showed that pannexin-1 channel is responsible for ATP secretion from autophagic dying Ba/F3 cells. MCF-7 and Ba/F3 cells dying with involvement of autophagy were capable of preventing crude LPS-induced pro-inflammatory cytokine release but pro-inflammatory cytokines were produced and secreted from human macrophages triggered by autophagic dying cells as a result of the secreted IL-1β. Finally, it was observed ... |
| نوع الوثيقة: |
other/unknown material |
| وصف الملف: |
application/msword; application/pdf |
| اللغة: |
English |
| Relation: |
http://hdl.handle.net/2437/130985 |
| الاتاحة: |
http://hdl.handle.net/2437/130985 |
| رقم الانضمام: |
edsbas.1CD3B9F8 |
| قاعدة البيانات: |
BASE |