Nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3
To the readers and editor,
We appreciate the comments by Yin et al. The focus of our study was to determine whether the nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3)-caspase 1 pathway played a role in the primed status of brain cells in aging brain and whether this primed status contributed to isoflurane-induced neuroinflammation and cognitive dysfunction. We provided in vitro and in vivo evidence for these effects. To implicate the role of NLRP3-caspase 1 pathway in the isoflurane effects, we used Ac-YVAD-cmk, a caspase 1 inhibitor, and NLRP3 siRNA. We feel confident that caspase 1 activity is important for the production of interleukin (IL)-18 and IL-1β and that NLRP3 activation is critical for isoflurane-induced caspase 1 activation. The evidence to support these points is in figure 2 and figure 6, respectively, of our publication .
We agree that MCC950 may be an additional tool to probe the role of NLPR3 in isoflurane effects. The proposal that pyroptosis contributes to isoflurane-induced cognitive impairment is interesting. However, our study did not show any effects on cell viability up to 12 h after NLRP3 was activated. However, it will be interesting to know whether NLRP3 inflammasome-dependent pyroptosis is involved in age-dependent isoflurane-induced cognitive impairment. These interesting ideas/proposals require experiments to test.
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