Differential requirement for the activation of the inflammasome for processing and release of IL-1β in monocytes and macrophages
The processing of pro-interleukin-1β depends on activation of caspase-1. Controversy has arisen whether Toll-like receptor (TLR) ligands alone can activate caspase-1 for release of interleukin-1β (IL-1β). Here we demonstrate that human blood monocytes release processed IL-1β after a one-time stimula...
Saved in:
Published in | Blood Vol. 113; no. 10; pp. 2324 - 2335 |
---|---|
Main Authors | , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Washington, DC
Elsevier Inc
05.03.2009
Americain Society of Hematology American Society of Hematology |
Series | Phagocytes, Granulocytes, and Myelopoiesis |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | The processing of pro-interleukin-1β depends on activation of caspase-1. Controversy has arisen whether Toll-like receptor (TLR) ligands alone can activate caspase-1 for release of interleukin-1β (IL-1β). Here we demonstrate that human blood monocytes release processed IL-1β after a one-time stimulation with either TLR2 or TLR4 ligands, resulting from constitutively activated caspase-1 and release of endogenous adenosine triphosphate. The constitutive activation of caspase-1 depends on the inflammasome components, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and NALP3, but in monocytes caspase-1 activation is uncoupled from pathogen-associated molecular pattern recognition. In contrast, macrophages are unable to process and release IL-1β solely by TLR ligands and require a second adenosine triphosphate stimulation. We conclude that IL-1β production is differentially regulated in monocytes and macrophages, and this reflects their separate functions in host defense and inflammation. |
---|---|
Bibliography: | C.A.N.-P. and M.F.N. contributed equally to this study. |
ISSN: | 0006-4971 1528-0020 |
DOI: | 10.1182/blood-2008-03-146720 |