Table 1.

Regulators of GSDMD activity

Mediator	Description	Effect	Reference
Disulfiram / NSA	Disulfiram modified the Cys191 residue of GSDMD, thereby inhibiting the pore-forming activity and liposome leakage of GSDMD	Disulfiram can inhibit IL-1β secretion in iBMDM and THP-1 cells, and improve the survival rate of mice with LPS-induced sepsis	[80, 81, 84]
DMF	DMF reacts with GSDMD at critical cysteine residues to form S-(2-succinyl)-cysteine	In mice, the administration of DMF protects against sepsis shock	[83]
TPNs	TPNs inhibit pyroptosis by blocking GSDMD-NT oligomerization	TPNs block canonical and noncanonical inflammasomes-induced pyroptosis in primary macrophages and THP-1 cells in a dose-dependent manner. TPNs treatment increases survival and body temperature in septic mice	[8]
Mg2+	Mg2+ blocks Ca2 + influx by inhibiting the ATP-gated Ca2 + channel P2X7, thereby impeding the function of GSDMD-NT	In HEK293T cells, Mg2 + inhibits GSDMD-NT membrane binding and oligomerization and protects against LPS-induced septic shock	[85]
IL-6	IL-6 inhibits caspase-3-GSDME and caspase-1-GSDMD	IL-6 protects streptococcus pneumoniae-induced pyroptosis and inflammatory injury in lung macrophages	[86]
TRIM21	The PRY-SPRY domain of TRIM21 interacts with GSDMD, maintains stable expression of GSDMD in the resting state, and induces GSDMD-N aggregation during pyroptosis	TRIM21-deficient cells have a reduced inflammasome-activated response, and mice with TRIM21 gene ablation are protected from LPS-induced inflammation and DSS-induced colitis	[87]

GSDMD Gasdermin D, DMF dimethyl fumarate, TPNs tea polyphenols nanoparticles, Cys191 191-position cysteine, HEK293T human embryonic kidney cells, IL-6 Interleukin 6, TRIM21 tripartite motif 21, DSS dextran sulfate sodium salt, LPS lipopolysaccharide