Inflammasome-independent modulation of cytokine response by autophagy in human cells.
Autophagy is a cell housekeeping mechanism that has recently received attention in relation to its effects on the immune response. Genetic studies have identified candidate loci for Crohn's disease susceptibility among autophagy genes, while experiments in murine macrophages from ATG16L1 defici...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3072416?pdf=render |
| _version_ | 1818609122180857856 |
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| author | Tania O Crişan Theo S Plantinga Frank L van de Veerdonk Marius F Farcaş Monique Stoffels Bart-Jan Kullberg Jos W M van der Meer Leo A B Joosten Mihai G Netea |
| author_facet | Tania O Crişan Theo S Plantinga Frank L van de Veerdonk Marius F Farcaş Monique Stoffels Bart-Jan Kullberg Jos W M van der Meer Leo A B Joosten Mihai G Netea |
| author_sort | Tania O Crişan |
| collection | DOAJ |
| description | Autophagy is a cell housekeeping mechanism that has recently received attention in relation to its effects on the immune response. Genetic studies have identified candidate loci for Crohn's disease susceptibility among autophagy genes, while experiments in murine macrophages from ATG16L1 deficient mice have shown that disruption of autophagy increases processing of IL-1β and IL-18 through an inflammasome-dependent manner. Using complementary approaches either inducing or inhibiting autophagy, we describe modulatory effects of autophagy on proinflammatory cytokine production in human cells. Inhibition of basal autophagy in human peripheral blood mononuclear cells (PBMCs) significantly enhances IL-1β after stimulation with TLR2 or TLR4 ligands, while at the same time reducing the production of TNFα. In line with this, induction of autophagy by starvation inhibited IL-1β production. These effects of autophagy were not exerted at the processing step, as inflammasome activation was not influenced. In contrast, the effect of autophagy on cytokine production was on transcription level, and possibly involving the inhibition of p38 mitogen activated protein kinase (MAPK) phosphorylation. In conclusion, autophagy modulates the secretion of proinflammatory cytokines in human cells through an inflammasome-independent pathway, and this is a novel mechanism that may be targeted in inflammatory diseases. |
| first_indexed | 2024-12-16T14:53:31Z |
| format | Article |
| id | doaj.art-fbf50f8105a14cbabda36fb413ff6dd1 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-16T14:53:31Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-fbf50f8105a14cbabda36fb413ff6dd12022-12-21T22:27:32ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0164e1866610.1371/journal.pone.0018666Inflammasome-independent modulation of cytokine response by autophagy in human cells.Tania O CrişanTheo S PlantingaFrank L van de VeerdonkMarius F FarcaşMonique StoffelsBart-Jan KullbergJos W M van der MeerLeo A B JoostenMihai G NeteaAutophagy is a cell housekeeping mechanism that has recently received attention in relation to its effects on the immune response. Genetic studies have identified candidate loci for Crohn's disease susceptibility among autophagy genes, while experiments in murine macrophages from ATG16L1 deficient mice have shown that disruption of autophagy increases processing of IL-1β and IL-18 through an inflammasome-dependent manner. Using complementary approaches either inducing or inhibiting autophagy, we describe modulatory effects of autophagy on proinflammatory cytokine production in human cells. Inhibition of basal autophagy in human peripheral blood mononuclear cells (PBMCs) significantly enhances IL-1β after stimulation with TLR2 or TLR4 ligands, while at the same time reducing the production of TNFα. In line with this, induction of autophagy by starvation inhibited IL-1β production. These effects of autophagy were not exerted at the processing step, as inflammasome activation was not influenced. In contrast, the effect of autophagy on cytokine production was on transcription level, and possibly involving the inhibition of p38 mitogen activated protein kinase (MAPK) phosphorylation. In conclusion, autophagy modulates the secretion of proinflammatory cytokines in human cells through an inflammasome-independent pathway, and this is a novel mechanism that may be targeted in inflammatory diseases.http://europepmc.org/articles/PMC3072416?pdf=render |
| spellingShingle | Tania O Crişan Theo S Plantinga Frank L van de Veerdonk Marius F Farcaş Monique Stoffels Bart-Jan Kullberg Jos W M van der Meer Leo A B Joosten Mihai G Netea Inflammasome-independent modulation of cytokine response by autophagy in human cells. PLoS ONE |
| title | Inflammasome-independent modulation of cytokine response by autophagy in human cells. |
| title_full | Inflammasome-independent modulation of cytokine response by autophagy in human cells. |
| title_fullStr | Inflammasome-independent modulation of cytokine response by autophagy in human cells. |
| title_full_unstemmed | Inflammasome-independent modulation of cytokine response by autophagy in human cells. |
| title_short | Inflammasome-independent modulation of cytokine response by autophagy in human cells. |
| title_sort | inflammasome independent modulation of cytokine response by autophagy in human cells |
| url | http://europepmc.org/articles/PMC3072416?pdf=render |
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