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Transcriptomic Prof...
Transcriptomic Profiling Reveals That HMGB1 Induces Macrophage Polarization Different from Classical M1
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Qu, HS (författare)
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- Heinback, R (författare)
- Karolinska Institutet
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Salo, H (författare)
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- Ewing, E (författare)
- Karolinska Institutet
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Espinosa, A (författare)
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- Aulin, C (författare)
- Karolinska Institutet
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- Harris, HE (författare)
- Karolinska Institutet
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(creator_code:org_t)
- 2022-06-02
- 2022
- Engelska.
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Ingår i: Biomolecules. - : MDPI AG. - 2218-273X. ; 12:6
- Relaterad länk:
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http://kipublication...
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https://doi.org/10.3...
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Abstract
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- Macrophages are key inflammatory immune cells that display dynamic phenotypes and functions in response to their local microenvironment. In different conditions, macrophage polarization can be induced by high-mobility group box 1 (HMGB1), a nuclear DNA-binding protein that activates innate immunity via the Toll-like receptor (TLR) 4, the receptor for advanced glycation end products (RAGE), and C-X-C chemokine receptor (CXCR) 4. This study investigated the phenotypes of murine bone-marrow-derived macrophages (BMDMs) stimulated with different HMGB1 redox isoforms using bulk RNA sequencing (RNA-Seq). Disulfide HMGB1 (dsHMGB1)-stimulated BMDMs showed a similar but distinct transcriptomic profile to LPS/IFNγ- and LPS-stimulated BMDMs. Fully reduced HMGB1 (frHMGB1) did not induce any significant transcriptomic change. Interestingly, compared to LPS/IFNγ- and LPS-, dsHMGB1-stimulated BMDMs showed lipid metabolism and foam cell differentiation gene set enrichment, and oil red O staining revealed that both dsHMGB1 and frHMGB1 alleviated oxidized low-density lipoprotein (oxLDL)-induced foam cells formation. Overall, this work, for the first time, used transcriptomic analysis by RNA-Seq to investigate the impact of HMGB1 stimulation on BMDM polarization. Our results demonstrated that dsHMGB1 and frHMGB1 induced distinct BMDM polarization phenotypes compared to LPS/IFNγ- and LPS- induced phenotypes.
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