The TLR4/TRIF-Mediated Activation of NLRP3 Inflammasome Underlies Endotoxin-Induced Liver Injury in Mice

Table 3

Requirement of MyD88 and TRIF for LPS sensitization and Caspase-1 activation, respectively. Mice with various genotypes were sequentially treated with P. acnes and LPS, and liver specimens and sera were sampled for histological analyses and measurement of IL-18/IL-1𝛽 levels by ELISA, respectively. Kupffer cells were incubated with LPS for 4 h, and each supernatant was collected for western blotting analyses and ELISA. Naïve mice have no hepatic granulomas or injuries, and their serum IL-18 and iL-1𝛽 were undetectable. Naïve Kupffer cells released no IL-18 and IL-1𝛽.

Genotype	Sensitization phase	Response to LPS
		In vivo		LPS-stimulated Kupffer cells
				Western blotting analyses		ELISA
	Granulomaformation^a	Liverinjury^b	Serum IL-18/IL-1𝛽^c(ELISA)	ProIL-1𝛽  production^d	ActiveCasp1^e	IL-1𝛽/IL-18 release^f
WT	+++	+++	+++	+++	+++	+++
𝑇𝑙𝑟4^−/−	+++	−	−	−	−	−
𝑀𝑦𝑑88^−/−	−	−	−	−	+++	++^𝑔
𝑇𝑟𝑖𝑓^−/−	+++	−	−	+++	−	−
𝐶𝑎𝑠𝑝1^−/−	+++	−	−	+++	−	−
𝐴𝑠𝑐^−/−	+++	−	−	+++	−	−
𝑁𝑙𝑟𝑝3^−/−	+++	−	−	ND	ND	−
𝑃2𝑥7𝑟^−/−	+++	+++	+++	+++	+++	+++

^a+++ indicates that 20% and more area of the liver section is occupied by granulomas; − indicates no granulomas.
^b+++ indicates more than 300 IU of serum ALT levels; − indicates normal range of them (< 50 IU).
^c+++ indicates more than 1000 and 50 pg/mL of serum IL-18 and IL-1𝛽 levels, respectively; − indicates normal range of them.
^d+++ indicates 10 times and more pro-IL-1𝛽 density in cell lysates; − indicates the absence of pro-IL-1𝛽.
^e+++ indicates the presence of active Caspase-1 (Casp1) in supernatant; − indicates the absence of it.
^f+++ indicates more than 100 pg/mL; − indicates undetectable levels.
^g++ indicates more than 50 pg/mL of IL-18, but undetectable IL-1𝛽.
ND; not done