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

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.