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25-Hydroxycholesterol acts as an amplifier of inflammatory signaling

Gold, Elizabeth S., Diercks, Alan H., Podolsky, Irina, Podyminogin, Rebecca L., Askovich, Peter S., Treuting, Piper M., Aderem, Alan·2014·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1404271111
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Abstract

Significance: The lipid 25-hydroxycholesterol (25HC) is produced by immune cells in response to infection. We demonstrate that in addition to interfering with viral entry and replication, 25HC also amplifies the activation of immune cells and increases the production of immune mediators. Furthermore, we show that the presence of 25HC is actually harmful in the setting of infection with influenza because the production of these immune mediators leads to damage to the host. These observations might have particular relevance for understanding the mechanisms behind the high pathogenicity of several recently emerged influenza strains, including the H5N1 “bird flu,” and might have implications for the protection of the host from these virulent strains.

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Crossref · 10.1073/pnas.1404271111

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  • Tau fibrils induce a proinflammatory response that is suppressed in the absence of Ch25h and 25-HC.

    “These in vitro data suggest that tau fibrils induce a proinflammatory response that is suppressed in the absence of Ch25h and 25-HC, similar to previous reports (Wong et al., 2020; Gold et al., 2014).”

    From Cholesterol 25-hydroxylase mediates neuroinflammation and neurodegeneration in a mouse model of tauopathy (2024) · cites this paper as Gold et al., 2014

    The Results and Discussion report that loss of Ch25h dampens inflammatory responses to polyI:C, other innate-immune receptor ligands, and infection, while 25HC amplifies those responses. This supports the cited analogy, but the paper does not test tau fibrils or establish that they induce a Ch25h-dependent response. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Gold et al. reported that 25-HC acts as an amplifier of inflammation in macrophages via an AP-1-mediated mechanism, contributing to tissue damage in mice following influenza infection.

    “Gold et al. reported that 25-HC acts as an amplifier of inflammation in macrophages via an AP-1-mediated mechanism, contributing to the tissue damage in mice following influenza infection [80].”

    From 25-Hydroxycholesterol amplifies microglial IL-1β production in an apoE isoform-dependent manner (2020) · cites this paper as [80]

  • CH25H deficient mice have decreased inflammatory-mediated pathology and death following influenza infection, reduced immune responses following experimental autoimmune encephalomyelitis (EAE), and in a mouse model of X-linked adrenoleukodystrophy (X-ALD).

    “CH25H deficient mice have also been shown to have decreased inflammatory-mediated pathology and death following influenza infection [80], reduced immune responses both following experimental autoimmune encephalomyelitis (EAE) [81] and in a mouse model of X-linked adrenoleukodystrophy (X-ALD) [82]”

    From 25-Hydroxycholesterol amplifies microglial IL-1β production in an apoE isoform-dependent manner (2020) · cites this paper as [80]

  • 25-HC has both anti-inflammatory and proinflammatory actions depending on the model system and context.

    “25-HC has also been reported to have both anti- (Reboldi et al., 2014; Dang et al., 2017) and proinflammatory (Gold et al., 2014; Fu et al., 2014) actions depending on the model system and context.”

    From Cholesterol 25-hydroxylase mediates neuroinflammation and neurodegeneration in a mouse model of tauopathy (2024) · cites this paper as Gold et al., 2014

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Research works printed but not linked: 40

  1. A Chawla, et al., PPAR-gamma dependent and independent effects on macrophage-gene expression in lipid metabolism and inflammation. Nat Med 7, 48–52 (2001). · DOI · Paper page
  2. S Ogawa, et al., Molecular determinants of crosstalk between nuclear receptors and toll-like receptors. Cell 122, 707–721 (2005). · DOI · Paper page
  3. A Castrillo, et al., Crosstalk between LXR and toll-like receptor signaling mediates bacterial and viral antagonism of cholesterol metabolism. Mol Cell 12, 805–816 (2003). · DOI
  4. C Jiang, AT Ting, B Seed, PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines. Nature 391, 82–86 (1998). · DOI · Paper page
  5. M Ricote, AC Li, TM Willson, CJ Kelly, CK Glass, The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation. Nature 391, 79–82 (1998). · DOI · Paper page
  6. ES Gold, et al., ATF3 protects against atherosclerosis by suppressing 25-hydroxycholesterol-induced lipid body formation. J Exp Med 209, 807–817 (2012). · DOI
  7. MS Brown, SE Dana, JL Goldstein, Cholesterol ester formation in cultured human fibroblasts. Stimulation by oxygenated sterols. J Biol Chem 250, 4025–4027 (1975). · DOI · Paper page
  8. MS Brown, JL Goldstein, A proteolytic pathway that controls the cholesterol content of membranes, cells, and blood. Proc Natl Acad Sci USA 96, 11041–11048 (1999). · DOI · Paper page
  9. Y Ma, et al., 25-Hydroxycholesterol-3-sulfate regulates macrophage lipid metabolism via the LXR/SREBP-1 signaling pathway. Am J Physiol Endocrinol Metab 295, E1369–E1379 (2008). · DOI
  10. SC Miller, G Melnykovych, Regulation of cholesterol biosynthesis and esterification by 25-hydroxycholesterol in a macrophage-like cell line: Uncoupling by progesterone. J Lipid Res 25, 991–999 (1984). · DOI
  11. JP Pereira, LM Kelly, JG Cyster, Finding the right niche: B-cell migration in the early phases of T-dependent antibody responses. Int Immunol 22, 413–419 (2010). · DOI
  12. T Yi, et al., Oxysterol gradient generation by lymphoid stromal cells guides activated B cell movement during humoral responses. Immunity 37, 535–548 (2012). · DOI
  13. J Ecker, et al., Induction of fatty acid synthesis is a key requirement for phagocytic differentiation of human monocytes. Proc Natl Acad Sci USA 107, 7817–7822 (2010). · DOI
  14. U Diczfalusy, et al., Marked upregulation of cholesterol 25-hydroxylase expression by lipopolysaccharide. J Lipid Res 50, 2258–2264 (2009). · DOI · Paper page
  15. K Park, AL Scott, Cholesterol 25-hydroxylase production by dendritic cells and macrophages is regulated by type I interferons. J Leukoc Biol 88, 1081–1087 (2010). · DOI
  16. M Blanc, et al., The transcription factor STAT-1 couples macrophage synthesis of 25-hydroxycholesterol to the interferon antiviral response. Immunity 38, 106–118 (2013). · DOI
  17. SY Liu, et al., Interferon-inducible cholesterol-25-hydroxylase broadly inhibits viral entry by production of 25-hydroxycholesterol. Immunity 38, 92–105 (2013). · DOI · Paper page
  18. DM Morens, AS Fauci, The 1918 influenza pandemic: Insights for the 21st century. J Infect Dis 195, 1018–1028 (2007). · DOI · Paper page
  19. IC Allen, et al., The NLRP3 inflammasome mediates in vivo innate immunity to influenza A virus through recognition of viral RNA. Immunity 30, 556–565 (2009). · DOI · Paper page
  20. T Kawai, S Akira, Antiviral signaling through pattern recognition receptors. J Biochem 141, 137–145 (2007). · DOI
  21. O Takeuchi, S Akira, Innate immunity to virus infection. Immunol Rev 227, 75–86 (2009). · DOI
  22. CM Rosenberger, et al., Characterization of innate responses to influenza virus infection in a novel lung type I epithelial cell model. J Gen Virol 95, 350–362 (2014). · DOI
  23. M Karin, Zg Liu, E Zandi, AP-1 function and regulation. Curr Opin Cell Biol 9, 240–246 (1997). · DOI
  24. J Hess, P Angel, M Schorpp-Kistner, AP-1 subunits: Quarrel and harmony among siblings. J Cell Sci 117, 5965–5973 (2004). · DOI
  25. EF Wagner, AP-1—Introductory remarks. Oncogene 20, 2334–2335 (2001). · DOI
  26. N Shibata, et al., 25-Hydroxycholesterol activates the integrated stress response to reprogram transcription and translation in macrophages. J Biol Chem 288, 35812–35823 (2013). · DOI
  27. CW Woo, et al., Adaptive suppression of the ATF4-CHOP branch of the unfolded protein response by toll-like receptor signalling. Nat Cell Biol 11, 1473–1480 (2009). · DOI
  28. CW Woo, L Kutzler, SR Kimball, I Tabas, Toll-like receptor activation suppresses ER stress factor CHOP and translation inhibition through activation of eIF2B. Nat Cell Biol 14, 192–200 (2012). · DOI
  29. M Goldfinger, M Shmuel, S Benhamron, B Tirosh, Protein synthesis in plasma cells is regulated by crosstalk between endoplasmic reticulum stress and mTOR signaling. Eur J Immunol 41, 491–502 (2011). · DOI
  30. G Clavarino, et al., Protein phosphatase 1 subunit Ppp1r15a/GADD34 regulates cytokine production in polyinosinic:polycytidylic acid-stimulated dendritic cells. Proc Natl Acad Sci USA 109, 3006–3011 (2012). · DOI
  31. N Cláudio, A Dalet, E Gatti, P Pierre, Mapping the crossroads of immune activation and cellular stress response pathways. EMBO J 32, 1214–1224 (2013). · DOI
  32. R Le Goffic, et al., Detrimental contribution of the Toll-like receptor (TLR)3 to influenza A virus-induced acute pneumonia. PLoS Pathog 2, e53 (2006). · DOI
  33. C Wilkins, M Gale, Sterol-izing innate immunity. Immunity 38, 3–5 (2013). · DOI
  34. JV Rajan, SE Warren, EA Miao, A Aderem, Activation of the NLRP3 inflammasome by intracellular poly I:C. FEBS Lett 584, 4627–4632 (2010). · DOI
  35. VC Tam, et al., Lipidomic profiling of influenza infection identifies mediators that induce and resolve inflammation. Cell 154, 213–227 (2013). · DOI
  36. RA Irizarry, et al., Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics 4, 249–264 (2003). · DOI · Paper page
  37. M Dai, et al., Evolving gene/transcript definitions significantly alter the interpretation of GeneChip data. Nucleic Acids Res 33, e175 (2005). · DOI
  38. X Lu, X Zhang, The effect of GeneChip gene definitions on the microarray study of cancers. Bioessays 28, 739–746 (2006). · DOI
  39. R Sandberg, O Larsson, Improved precision and accuracy for microarrays using updated probe set definitions. BMC Bioinformatics 8, 48 (2007). · DOI
  40. JA Rutigliano, et al., Highly pathological influenza A virus infection is associated with augmented expression of PD-1 by functionally compromised virus-specific CD8+ T cells. J Virol 88, 1636–1651 (2014). · DOI

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Metadata

Authors
Gold, E. S., Diercks, A. H., Podolsky, I., Podyminogin, R. L., Askovich, P. S., Treuting, P. M., & Aderem, A.
Affiliations
  • Seattle Biomedical Research Institute, Seattle, WA 98109; and
  • Department of Comparative Medicine, University of Washington, Seattle, WA 98195
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2014-07-03
Volume
111
Issue
29
Pages
10666-10671
ISSN
  • 0027-8424
  • 1091-6490
DOI
10.1073/pnas.1404271111
Cited by
250
References
4
Language
en

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