Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
권호 표지
DOI QR코드

DOI QR Code

Prolonged Exposure to Lipopolysaccharide Induces NLRP3-Independent Maturation and Secretion of Interleukin (IL)-1β in Macrophages

  • Hong, Sujeong (Department of Microbiology and Immunology, Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine) ;
  • Yu, Je-Wook (Department of Microbiology and Immunology, Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine)
  • Received : 2017.09.12
  • Accepted : 2017.10.15
  • Published : 2018.01.28
Download PDF
⟨ Previous Next ⟩

Abstract

Upon sensing of microbial infections or endogenous danger signals in macrophages, inflammasome signaling plays a significant role in triggering inflammatory responses via producing interleukin (IL)-$1{\beta}$. Recent studies revealed that active caspase-1, a product of the inflammasome complex, causes maturation of inactive pro-IL-$1{\beta}$ into the active form. However, the underlying mechanism by which this leaderless cytokine is secreted into the extracellular space remains to be elucidated. In this study, we demonstrated that prolonged lipopolysaccharide (LPS) treatment to macrophages could trigger the unexpected maturation and extracellular release of IL-$1{\beta}$ through a nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3 (NLRP3)-independent manner. Short-term treatment (less than 6 h) of LPS induced robust production of the IL-$1{\beta}$ precursor form inside cells but did not promote the maturation and secretion of IL-$1{\beta}$ in bone marrow-derived macrophages or peritoneal macrophages. Instead, prolonged LPS treatment (more than 12 h) led to a significant release of matured IL-$1{\beta}$ with no robust indication of caspase-1 activation. Intriguingly, this LPS-triggered secretion of IL-$1{\beta}$ was also observed in NLRP3-deficient macrophages. In addition, this unexpected IL-$1{\beta}$ release was only partially impaired by a caspase-1 and NLRP3 inflammasome inhibitor. Collectively, our results propose that prolonged exposure to LPS is able to drive the maturation and secretion of IL-$1{\beta}$ in an NLRP3 inflammasome-independent manner.

Keywords

References

  1. Dinarello CA. 2011. Interleukin-1 in the pathogenesis and treatment of inflammatory diseases. Blood 117: 3720-3732.
  2. Rubartelli A, Cozzolino F, Talio M, Sitia R. 1990. A novel secretory pathway for interleukin-1 beta, a protein lacking a signal sequence. EMBO J. 9: 1503-1510.
  3. Thornberry NA, Bull HG, Calaycay JR, Chapman KT, Howard AD, Kostura MJ, et al. 1992. A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes. Nature 356: 768-774.
  4. Keller M, Ruegg A, Werner S, Beer HD. 2008. Active caspase-1 is a regulator of unconventional protein secretion. Cell 132: 818-831. https://doi.org/10.1016/j.cell.2007.12.040
  5. Agostini L, Martinon F, Burns K, McDermott MF, Hawkins PN, Tschopp J. 2004. NALP3 forms an IL-1beta-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder. Immunity 20: 319-325. https://doi.org/10.1016/S1074-7613(04)00046-9
  6. Fernandes-Alnemri T, Yu JW, Datta P, Wu J, Alnemri ES. 2009. AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA. Nature 458: 509-513. https://doi.org/10.1038/nature07710
  7. Latz E, Xiao TS, Stutz A. 2013. Activation and regulation of the inflammasomes. Nat. Rev. Immunol. 13: 397-411. https://doi.org/10.1038/nri3452
  8. Yu JW, Lee MS. 2016. Mitochondria and the NLRP3 inflammasome: physiological and pathological relevance. Arch. Pharm. Res. 39: 1503-1518. https://doi.org/10.1007/s12272-016-0827-4
  9. Haneklaus M, O'Neill LA, Coll RC. 2013. Modulatory mechanisms controlling the NLRP3 inflammasome in inflammation: recent developments. Curr. Opin. Immunol. 25:40-45.
  10. Ghonime MG, Shamaa OR, Das S, Eldomany RA, Fernandes-Alnemri T, Alnemri ES, et al. 2014. Inflammasome priming by lipopolysaccharide is dependent upon ERK signaling and proteasome function. J. Immunol. 192: 3881-3888. https://doi.org/10.4049/jimmunol.1301974
  11. Juliana C, Fernandes-Alnemri T, Kang S, Farias A, Qin F, Alnemri ES. 2012. Non-transcriptional priming and deubiquitination regulate NLRP3 inflammasome activation. J. Biol. Chem. 287: 36617-36622. https://doi.org/10.1074/jbc.M112.407130
  12. Fernandes-Alnemri T, Kang S, Anderson C, Sagara J, Fitzgerald KA, Alnemri ES. 2013. Cutting edge: TLR signaling licenses IRAK1 for rapid activation of the NLRP3 inflammasome. J. Immunol. 191: 3995-3999. https://doi.org/10.4049/jimmunol.1301681
  13. He Y, Franchi L, Nunez G. 2013. TLR agonists stimulate Nlrp3-dependent IL-1beta production independently of the purinergic P2X7 receptor in dendritic cells and in vivo. J. Immunol. 190: 334-339. https://doi.org/10.4049/jimmunol.1202737
  14. Hwang I, Yang J, Hong S, Lee EJ, Lee SH, Fernandes-Alnemri T, et al. 2015. Non-transcriptional regulation of NLRP3 inflammasome signaling by IL-4. Immunol. Cell Biol. 93: 591-599. https://doi.org/10.1038/icb.2014.125
  15. Vigano E, Diamond CE, Spreafico R, Balachander A, Sobota RM, Mortellaro A. 2015. Human caspase-4 and caspase-5 regulate the one-step non-canonical inflammasome activation in monocytes. Nat. Commun. 6: 8761. https://doi.org/10.1038/ncomms9761
  16. Tateda K, Matsumoto T, Miyazaki S, Yamaguchi K. 1996. Lipopolysaccharide-induced lethality and cytokine production in aged mice. Infect. Immun. 64: 769-774.
  17. Eltom S, Belvisi MG, Yew-Booth L, Dekkak B, Maher SA, Dubuis ED, et al. 2014. TLR4 activation induces IL-1beta release via an IPAF dependent but caspase 1/11/8 independent pathway in the lung. Respir. Res. 15: 87. https://doi.org/10.1186/s12931-014-0087-0
  18. Yu JW, Fernandes-Alnemri T, Datta P, Wu J, Juliana C, Solorzano L, et al. 2007. Pyrin activates the ASC pyroptosome in response to engagement by autoinflammatory PSTPIP1 mutants. Mol. Cell 28: 214-227. https://doi.org/10.1016/j.molcel.2007.08.029
  19. Fernandes-Alnemri T, Wu J, Yu JW, Datta P, Miller B, Jankowski W, et al. 2007. The pyroptosome: a supramolecular assembly of ASC dimers mediating inflammatory cell death via caspase-1 activation. Cell Death Differ. 14: 1590-1604. https://doi.org/10.1038/sj.cdd.4402194
  20. Broz P, Dixit VM. 2016. Inflammasomes: mechanism of assembly, regulation and signalling. Nat. Rev. Immunol. 16: 407-420. https://doi.org/10.1038/nri.2016.58
  21. Mariathasan S, Monack DM. 2007. Inflammasome adaptors and sensors: intracellular regulators of infection and inflammation. Nat. Rev. Immunol. 7: 31-40. https://doi.org/10.1038/nri1997
  22. Py BF, Kim MS, Vakifahmetoglu-Norberg H, Yuan J. 2013. Deubiquitination of NLRP3 by BRCC3 critically regulates inflammasome activity. Mol. Cell 49: 331-338. https://doi.org/10.1016/j.molcel.2012.11.009
  23. Kayagaki N, Wong MT, Stowe IB, Ramani SR, Gonzalez LC, Akashi-Takamura S, et al. 2013. Noncanonical inflammasome activation by intracellular LPS independent of TLR4. Science 341: 1246-1249.
  24. Hagar JA, Powell DA, Aachoui Y, Ernst RK, Miao EA. 2013. Cytoplasmic LPS activates caspase-11: implications in TLR4-independent endotoxic shock. Science 341: 1250-1253. https://doi.org/10.1126/science.1240988
  25. Stammler D, Eigenbrod T, Menz S, Frick JS, Sweet MJ, Shakespear MR, et al. 2015. Inhibition of histone deacetylases permits lipopolysaccharide-mediated secretion of bioactive IL-1beta via a caspase-1-independent mechanism. J. Immunol. 195: 5421-5431. https://doi.org/10.4049/jimmunol.1501195

Cited by

  1. Role of Muramyl Dipeptide in Lipopolysaccharide-Mediated Biological Activity and Osteoclast Activity vol.2018, pp.None, 2018, https://doi.org/10.1155/2018/8047610
  2. Pterostilbene Protects Against Lipopolysaccharide/D-Galactosamine-Induced Acute Liver Failure by Upregulating the Nrf2 Pathway and Inhibiting NF- κ B, MAPK, and NLRP3 Inflammasome Activation vol.23, pp.9, 2018, https://doi.org/10.1089/jmf.2019.4647