Cargando…
HSP70-Homolog DnaK of Pseudomonas aeruginosa Increases the Production of IL-27 through Expression of EBI3 via TLR4-Dependent NF-κB and TLR4-Independent Akt Signaling
IL-27, a heterodimeric cytokine composed of the p28 subunit and Epstein–Barr virus-induced gene 3 (EBI3), acts as a potent immunosuppressant and thus limits pathogenic inflammatory responses. IL-27 is upregulated upon Pseudomonas aeruginosa infection in septic mice, increasing susceptibility to the...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730953/ https://www.ncbi.nlm.nih.gov/pubmed/33276561 http://dx.doi.org/10.3390/ijms21239194 |
_version_ | 1783621803561713664 |
---|---|
author | Jeon, Jisu Lee, Yeji Yu, Hyeonseung Ha, Un-Hwan |
author_facet | Jeon, Jisu Lee, Yeji Yu, Hyeonseung Ha, Un-Hwan |
author_sort | Jeon, Jisu |
collection | PubMed |
description | IL-27, a heterodimeric cytokine composed of the p28 subunit and Epstein–Barr virus-induced gene 3 (EBI3), acts as a potent immunosuppressant and thus limits pathogenic inflammatory responses. IL-27 is upregulated upon Pseudomonas aeruginosa infection in septic mice, increasing susceptibility to the infection and decreasing clearance of the pathogen. However, it remains unclear which P. aeruginosa-derived molecules promote production of IL-27. In this study, we explored the mechanism by which P. aeruginosa DnaK, a heat shock protein 70-like protein, induces EBI3 expression, thereby promoting production of IL-27. Upregulation of EBI3 expression did not lead to an increase in IL-35, which consists of the p35 subunit and EBI3. The IL-27 production in response to DnaK was biologically active, as reflected by stimulation of IL-10 production. DnaK-mediated expression of EBI3 was driven by two distinct signaling pathways, NF-κB and Akt. However, NF-κB is linked to TLR4-associated signaling pathways, whereas Akt is not. Taken together, our results reveal that P. aeruginosa DnaK potently upregulates EBI3 expression, which in turn drives production of the prominent anti-inflammatory cytokine IL-27, as a consequence of TLR4-dependent activation of NF-κB and TLR4-independent activation of the Akt signaling pathway. |
format | Online Article Text |
id | pubmed-7730953 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-77309532020-12-12 HSP70-Homolog DnaK of Pseudomonas aeruginosa Increases the Production of IL-27 through Expression of EBI3 via TLR4-Dependent NF-κB and TLR4-Independent Akt Signaling Jeon, Jisu Lee, Yeji Yu, Hyeonseung Ha, Un-Hwan Int J Mol Sci Article IL-27, a heterodimeric cytokine composed of the p28 subunit and Epstein–Barr virus-induced gene 3 (EBI3), acts as a potent immunosuppressant and thus limits pathogenic inflammatory responses. IL-27 is upregulated upon Pseudomonas aeruginosa infection in septic mice, increasing susceptibility to the infection and decreasing clearance of the pathogen. However, it remains unclear which P. aeruginosa-derived molecules promote production of IL-27. In this study, we explored the mechanism by which P. aeruginosa DnaK, a heat shock protein 70-like protein, induces EBI3 expression, thereby promoting production of IL-27. Upregulation of EBI3 expression did not lead to an increase in IL-35, which consists of the p35 subunit and EBI3. The IL-27 production in response to DnaK was biologically active, as reflected by stimulation of IL-10 production. DnaK-mediated expression of EBI3 was driven by two distinct signaling pathways, NF-κB and Akt. However, NF-κB is linked to TLR4-associated signaling pathways, whereas Akt is not. Taken together, our results reveal that P. aeruginosa DnaK potently upregulates EBI3 expression, which in turn drives production of the prominent anti-inflammatory cytokine IL-27, as a consequence of TLR4-dependent activation of NF-κB and TLR4-independent activation of the Akt signaling pathway. MDPI 2020-12-02 /pmc/articles/PMC7730953/ /pubmed/33276561 http://dx.doi.org/10.3390/ijms21239194 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Jeon, Jisu Lee, Yeji Yu, Hyeonseung Ha, Un-Hwan HSP70-Homolog DnaK of Pseudomonas aeruginosa Increases the Production of IL-27 through Expression of EBI3 via TLR4-Dependent NF-κB and TLR4-Independent Akt Signaling |
title | HSP70-Homolog DnaK of Pseudomonas aeruginosa Increases the Production of IL-27 through Expression of EBI3 via TLR4-Dependent NF-κB and TLR4-Independent Akt Signaling |
title_full | HSP70-Homolog DnaK of Pseudomonas aeruginosa Increases the Production of IL-27 through Expression of EBI3 via TLR4-Dependent NF-κB and TLR4-Independent Akt Signaling |
title_fullStr | HSP70-Homolog DnaK of Pseudomonas aeruginosa Increases the Production of IL-27 through Expression of EBI3 via TLR4-Dependent NF-κB and TLR4-Independent Akt Signaling |
title_full_unstemmed | HSP70-Homolog DnaK of Pseudomonas aeruginosa Increases the Production of IL-27 through Expression of EBI3 via TLR4-Dependent NF-κB and TLR4-Independent Akt Signaling |
title_short | HSP70-Homolog DnaK of Pseudomonas aeruginosa Increases the Production of IL-27 through Expression of EBI3 via TLR4-Dependent NF-κB and TLR4-Independent Akt Signaling |
title_sort | hsp70-homolog dnak of pseudomonas aeruginosa increases the production of il-27 through expression of ebi3 via tlr4-dependent nf-κb and tlr4-independent akt signaling |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730953/ https://www.ncbi.nlm.nih.gov/pubmed/33276561 http://dx.doi.org/10.3390/ijms21239194 |
work_keys_str_mv | AT jeonjisu hsp70homologdnakofpseudomonasaeruginosaincreasestheproductionofil27throughexpressionofebi3viatlr4dependentnfkbandtlr4independentaktsignaling AT leeyeji hsp70homologdnakofpseudomonasaeruginosaincreasestheproductionofil27throughexpressionofebi3viatlr4dependentnfkbandtlr4independentaktsignaling AT yuhyeonseung hsp70homologdnakofpseudomonasaeruginosaincreasestheproductionofil27throughexpressionofebi3viatlr4dependentnfkbandtlr4independentaktsignaling AT haunhwan hsp70homologdnakofpseudomonasaeruginosaincreasestheproductionofil27throughexpressionofebi3viatlr4dependentnfkbandtlr4independentaktsignaling |