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A high concentration of DMSO activates caspase-1 by increasing the cell membrane permeability of potassium

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Abstract

Dimethyl sulfoxide (DMSO) is widely used in the laboratory and in clinical situations because it is soluble in both aqueous and organic media and can be used to treat many types of diseases. Thus, it is meaningful to assess the comprehensive and in-depth biological activities of DMSO. Here, we showed that a high concentration of DMSO induced pro-inflammatory cytokine interleukin-1β (IL-1β) secretion from the monocytic cell line THP-1. DMSO-induced IL-1β secretion was dependent on intracellular caspase-1 activation. Further study revealed that the activation of caspase-1 by DMSO relied on NLRP3 inflammasome formation. It is generally accepted that the NLRP3 inflammasome is activated by reactive oxygen species generation or potassium efflux; however, the common NLRP3 inflammasome trigger remains controversial. Here, we showed that although DMSO is a ROS scavenger, this chemical increases membrane permeability and potassium efflux, and the formation of the NLRP3 inflammasome reflects the increased membrane permeability and potassium efflux induced by DMSO. The present study reveals a new characteristic of DMSO, which should be considered when using this chemical in either the laboratory or the clinic.

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References

  • Aita K, Irie H, Tanuma Y, Toida S, Okuma Y, Mori S, Shiga J (2005) Apoptosis in murine lymphoid organs following intraperitoneal administration of dimethyl sulfoxide (DMSO). Exp Mol Pathol 79:265–271

    Article  CAS  Google Scholar 

  • Alvarez S, Munoz-Fernandez MA (2013) TNF-Alpha may mediate inflammasome activation in the absence of bacterial infection in more than one way. PLoS ONE 8:e71477

    Article  CAS  Google Scholar 

  • Bock M, Schleuning M, Heim MU, Mempel W (1995) Cryopreservation of human platelets with dimethyl sulfoxide: changes in biochemistry and cell function. Transfusion 35:921–924

    Article  CAS  Google Scholar 

  • Chen M, Wang H, Chen W, Meng G (2011) Regulation of adaptive immunity by the NLRP3 inflammasome. Int Immunopharmacol 11:549–554

    Article  CAS  Google Scholar 

  • Davis JM, Rowley SD, Braine HG, Piantadosi S, Santos GW (1990) Clinical toxicity of cryopreserved bone marrow graft infusion. Blood 75:781–786

    CAS  Google Scholar 

  • Essani NA, Fisher MA, Jaeschke H (1997) Inhibition of NF-kappa B activation by dimethyl sulfoxide correlates with suppression of TNF-alpha formation, reduced ICAM-1 gene transcription, and protection against endotoxin-induced liver injury. Shock 7:90–96

    Article  CAS  Google Scholar 

  • Franchi L, Munoz-Planillo R, Nunez G (2012) Sensing and reacting to microbes through the inflammasomes. Nat Immunol 13:325–332

    Article  CAS  Google Scholar 

  • Hanslick JL, Lau K, Noguchi KK, Olney JW, Zorumski CF, Mennerick S, Farber NB (2009) Dimethyl sulfoxide (DMSO) produces widespread apoptosis in the developing central nervous system. Neurobiol Dis 34:1–10

    Article  CAS  Google Scholar 

  • Hise AG, Tomalka J, Ganesan S, Patel K, Hall BA, Brown GD, Fitzgerald KA (2009) An essential role for the NLRP3 inflammasome in host defense against the human fungal pathogen Candida albicans. Cell Host Microbe 5:487–497

    Article  CAS  Google Scholar 

  • Hsieh SD, Yamamoto R, Saito K, Iwamoto Y, Kuzuya T, Ohba S, Kobori S, Saito K (1987) Amyloidosis presented with whitening and loss of hair which improved after dimethylsulfoxide (DMSO) treatment. Japanese J Med 26:393–395

    Article  CAS  Google Scholar 

  • Iwasaki T, Hamano T, Aizawa K, Kobayashi K, Kakishita E (1994) A case of pulmonary amyloidosis associated with multiple myeloma successfully treated with dimethyl sulfoxide. Acta Haematol 91:91–94

    Article  CAS  Google Scholar 

  • Joly S, Sutterwala FS (2010) Fungal pathogen recognition by the NLRP3 inflammasome. Virulence 1:276–280

    Article  Google Scholar 

  • Joshi VD, Kalvakolanu DV, Hebel JR, Hasday JD, Cross AS (2002) Role of caspase 1 in murine antibacterial host defenses and lethal endotoxemia. Infect Immun 70:6896–6903

    Article  CAS  Google Scholar 

  • Keller M, Ruegg A, Werner S, Beer HD (2008) Active caspase-1 is a regulator of unconventional protein secretion. Cell 132:818–831

    Article  CAS  Google Scholar 

  • Lee GS, Subramanian N, Kim AI, Aksentijevich I, Goldbach-Mansky R, Sacks DB, Germain RN, Kastner DL, Chae JJ (2012) The calcium-sensing receptor regulates the NLRP3 inflammasome through Ca2+ and cAMP. Nature 492:123–127

    Article  CAS  Google Scholar 

  • Lima H Jr, Jacobson LS, Goldberg MF, Chandran K, Diaz-Griffero F, Lisanti MP, Brojatsch J (2013) Role of lysosome rupture in controlling Nlrp3 signaling and necrotic cell death. Cell Cycle 12:1868–1878

    Article  CAS  Google Scholar 

  • Liu J, Yoshikawa H, Nakajima Y, Tasaka K (2001) Involvement of mitochondrial permeability transition and caspase-9 activation in dimethyl sulfoxide-induced apoptosis of EL-4 lymphoma cells. Int Immunopharmacol 1:63–74

    Article  CAS  Google Scholar 

  • Liu SB, He YY, Zhang Y, Lee WH, Qian JQ, Lai R, Jin Y (2008) A novel non-lens betagamma-crystallin and trefoil factor complex from amphibian skin and its functional implications. PLoS ONE 3:e1770

    Article  Google Scholar 

  • Martinon F, Burns K, Tschopp J (2002) The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol Cell 10:417–426

    Article  CAS  Google Scholar 

  • Masson MJ, Carpenter LD, Graf ML, Pohl LR (2008) Pathogenic role of natural killer T and natural killer cells in acetaminophen-induced liver injury in mice is dependent on the presence of dimethyl sulfoxide. Hepatology 48:889–897

    Article  CAS  Google Scholar 

  • McCammon KA, Lentzner AN, Moriarty RP, Schellhammer PF (1998) Intravesical dimethyl sulfoxide for primary amyloidosis of the bladder. Urology 52:1136–1138

    Article  CAS  Google Scholar 

  • Menu P, Vince JE (2011) The NLRP3 inflammasome in health and disease: the good, the bad and the ugly. Clin Exp Immunol 166:1–15

    Article  CAS  Google Scholar 

  • Misawa T, Takahama M, Kozaki T, Lee H, Zou J, Saitoh T, Akira S (2013) Microtubule-driven spatial arrangement of mitochondria promotes activation of the NLRP3 inflammasome. Nat Immunol 14:454–460

    Article  CAS  Google Scholar 

  • Munoz-Planillo R, Kuffa P, Martinez-Colon G, Smith BL, Rajendiran TM, Nunez G (2013) K(+) efflux is the common trigger of NLRP3 inflammasome activation by bacterial toxins and particulate matter. Immunity 38:1142–1153

    Article  CAS  Google Scholar 

  • Murav’ev Iu V, Opaleva GN, Manuilova LS (1990) Evaluation of the effect of dimethyl sulfoxide on experimental amyloidosis. Revmatologiia (Mosk) 44–46

  • Ogura Y, Sutterwala FS, Flavell RA (2006) The inflammasome: first line of the immune response to cell stress. Cell 126:659–662

    Article  CAS  Google Scholar 

  • Peeters PM, Perkins TN, Wouters EF, Mossman BT, Reynaert NL (2013) Silica induces NLRP3 inflammasome activation in human lung epithelial cells. Particle and fibre toxicology 10:3

    Article  CAS  Google Scholar 

  • Santos NC, Figueira-Coelho J, Martins-Silva J, Saldanha C (2003) Multidisciplinary utilization of dimethyl sulfoxide: pharmacological, cellular, and molecular aspects. Biochem Pharmacol 65:1035–1041

    Article  CAS  Google Scholar 

  • Schroder K, Tschopp J (2010) The inflammasomes. Cell 140:821–832

    Article  CAS  Google Scholar 

  • Shio MT, Eisenbarth SC, Savaria M, Vinet AF, Bellemare MJ, Harder KW, Sutterwala FS, Bohle DS, Descoteaux A, Flavell RA, Olivier M (2009) Malarial hemozoin activates the NLRP3 inflammasome through Lyn and Syk kinases. PLoS Pathog 5:e1000559

    Article  Google Scholar 

  • Tschopp J, Schroder K (2010) NLRP3 inflammasome activation: the convergence of multiple signalling pathways on ROS production? Nat Rev Immunol 10:210–215

    Article  CAS  Google Scholar 

  • Vance RE (2010) Inflammasome activation: how macrophages watch what they eat. Cell Host Microbe 7:3–5

    Article  CAS  Google Scholar 

  • Xiang Y, Gao Q, Su W, Zeng L, Wang J, Hu Y, Nie W, Ma X, Zhang Y, Lee W (2012) Establishment, characterization and immortalization of a fibroblast cell line from the Chinese red belly toad Bombina maxima skin. Cytotechnology 64:95–105

    Article  CAS  Google Scholar 

  • Xiang Y, Wang X, Yan C, Gao Q, Li SA, Liu J, Zhou K, Guo X, Lee W, Zhang Y (2013) Adenosine-5′-triphosphate (ATP) protects mice against bacterial infection by activation of the NLRP3 inflammasome. PLoS ONE 8:e63759

    Article  CAS  Google Scholar 

  • Xing L, Remick DG (2005) Mechanisms of dimethyl sulfoxide augmentation of IL-1 beta production. J Immunol 174:6195–6202

    Article  CAS  Google Scholar 

  • Xiang Y, Yan C, Guo X, Zhou K, Li S, Gao Q, Wang X, Zhao F, Liu J, Lee W-H, Zhang Y (2014) Host-derived, pore-forming toxin-like protein and trefoil factor complex protects the host against microbial infection. Proc Natl Acad Sci 111:6702–6707

  • Zhang Y (2015) Why do we study animal toxins? Dongwuxue Yanjiu 36:183–222

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Acknowledgements

This work was financially supported by the National Natural Science Foundation of China to Yang Xiang (91649120) and Sujiao Sun (81560697), Applied and basic research project of Yunnan Province (2014FB175) to Yang Xiang, and "Yunnan scholar" Program to Yun Zhang.

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Correspondence to Yang Xiang or Yun Zhang.

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Xiang, Y., Zhao, Mm., Sun, S. et al. A high concentration of DMSO activates caspase-1 by increasing the cell membrane permeability of potassium. Cytotechnology 70, 313–320 (2018). https://doi.org/10.1007/s10616-017-0145-9

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