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@ARTICLE{Wang:272488,
      author       = {Wang, Wei and Dernst, Alesja and Martin, Bianca and
                      Lorenzi, Lucia and Cadefau-Fabregat, Maria and Phulphagar,
                      Kshiti and Wagener, Antonia and Budden, Christina and Stair,
                      Neil and Wagner, Theresa and Färber, Harald and Jaensch,
                      Andreas and Stahl, Rainer and Duthie, Fraser and Schmidt,
                      Susanne V and Coll, Rebecca C and Meissner, Felix and
                      Cuartero, Sergi and Latz, Eicke and Mangan, Matthew},
      title        = {{B}utyrate and propionate are microbial danger signals that
                      activate the {NLRP}3 inflammasome in human macrophages upon
                      {TLR} stimulation.},
      journal      = {Cell reports},
      volume       = {43},
      number       = {9},
      issn         = {2211-1247},
      address      = {[New York, NY]},
      publisher    = {Elsevier},
      reportid     = {DZNE-2024-01169},
      pages        = {114736},
      year         = {2024},
      abstract     = {Short-chain fatty acids (SCFAs) are immunomodulatory
                      compounds produced by the microbiome through dietary fiber
                      fermentation. Although generally considered beneficial for
                      gut health, patients suffering from inflammatory bowel
                      disease (IBD) display poor tolerance to fiber-rich diets,
                      suggesting that SCFAs may have contrary effects under
                      inflammatory conditions. To investigate this, we examined
                      the effect of SCFAs on human macrophages in the presence of
                      Toll-like receptor (TLR) agonists. In contrast to
                      anti-inflammatory effects under steady-state conditions, we
                      found that butyrate and propionate activated the NOD-, LRR-,
                      and pyrin domain-containing protein 3 (NLRP3) inflammasome
                      in the presence of TLR agonists. Mechanistically, these
                      SCFAs prevented transcription of FLICE-like inhibitory
                      protein (cFLIP) and interleukin-10 (IL-10) through histone
                      deacetylase (HDAC) inhibition, triggering
                      caspase-8-dependent NLRP3 inflammasome activation.
                      SCFA-driven NLRP3 activation was potassium efflux
                      independent and did not result in cell death but rather
                      triggered hyperactivation and IL-1β release. Our findings
                      demonstrate that butyrate and propionate are bacterially
                      derived danger signals that regulate NLRP3 inflammasome
                      activation through epigenetic modulation of the inflammatory
                      response.},
      keywords     = {Humans / NLR Family, Pyrin Domain-Containing 3 Protein:
                      metabolism / Inflammasomes: metabolism / Propionates:
                      pharmacology / Butyrates: pharmacology / Macrophages:
                      metabolism / Macrophages: drug effects / Toll-Like
                      Receptors: metabolism / Signal Transduction: drug effects /
                      Interleukin-1beta: metabolism / Interleukin-10: metabolism /
                      CP: Immunology (Other) / HDAC (Other) / IL-10 (Other) /
                      NLRP3 (Other) / SCFA (Other) / acetylation (Other) /
                      butyrate (Other) / cFLIP (Other) / caspase-8 (Other) /
                      inflammasome (Other) / propionate (Other) / NLR Family,
                      Pyrin Domain-Containing 3 Protein (NLM Chemicals) /
                      Inflammasomes (NLM Chemicals) / Propionates (NLM Chemicals)
                      / Butyrates (NLM Chemicals) / Toll-Like Receptors (NLM
                      Chemicals) / NLRP3 protein, human (NLM Chemicals) /
                      Interleukin-1beta (NLM Chemicals) / Interleukin-10 (NLM
                      Chemicals)},
      cin          = {AG Latz},
      ddc          = {610},
      cid          = {I:(DE-2719)1013024},
      pnm          = {351 - Brain Function (POF4-351)},
      pid          = {G:(DE-HGF)POF4-351},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39277863},
      doi          = {10.1016/j.celrep.2024.114736},
      url          = {https://pub.dzne.de/record/272488},
}