HSP70-Homolog DnaK of Pseudomonas aeruginosa Increases the Production of IL-27 through Expression of EBI3 via TLR4-Dependent NF-kappa B and TLR4-Independent Akt Signaling
- Authors
- Jeon, Jisu; Lee, Yeji; Yu, Hyeonseung; Ha, Un-Hwan
- Issue Date
- 12월-2020
- Publisher
- MDPI
- Keywords
- Akt; DnaK; EBI3; IL-27; NF-& #954; B; Pseudomonas aeruginosa; TLR4
- Citation
- INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v.21, no.23
- Indexed
- SCIE
SCOPUS
- Journal Title
- INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
- Volume
- 21
- Number
- 23
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/51330
- DOI
- 10.3390/ijms21239194
- ISSN
- 1661-6596
- Abstract
- 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-kappa B and Akt. However, NF-kappa B 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-kappa B and TLR4-independent activation of the Akt signaling pathway.
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