In fibrotic NASH, treatment with miR-223 3p led to a remarkable mitigation of fibrosis development and activation of hepatic stellate cells (HSCs). miR-223 3p disrupted the activation of the NLRP3 inflammasome by impairing the synthesis of cleaved interleukin-1β (IL-1β), mature IL-1β, and NLRP3, and the activation of caspase-1 p10 in both EAH and fibrotic NASH.
Secondly, the results of IHC staining indicated that the expressions of CLS1 and NLRP3 in liver tissues were significantly upregulated in the NASH group compared to the ND group.
Taken together, our findings demonstrated that inhibited the activation of the TXNIP-NLRP3 axis reduced MPO activity and oxidative stress and thus restoring the intestinal barrier function in NASH.
NLRP3, ASC and Caspase-1 protein expression levels in KCs from NASH mouse livers were significantly higher than those in KCs from NLRP3<sup>-/-</sup> mice, and the number of NLRP3 inflammasome protein complexes was significantly higher in KCs from NASH mouse livers, whereas these protein complexes could not be formed in NLRP3<sup>-/-</sup> mice.
In conclusion, the suppression of the NLRP3/6 inflammasome pathway and NF-κB activation may partly contribute to the reduction of the hepatic injury during the progression of NASH by therapeutic LBP treatment.
NLRP3-/- mice exhibited less severe NASH than WT mice in MCD diet model, whereas TXNIP deficiency enhanced NLRP3 inflammasome activation and exacerbated liver injury.
This study aimed at investigating the role of the purinergic receptor 2X<sub>7</sub> (PR2X<sub>7</sub>), through the NLRP3 inflammasome, in the development of NASH.
Thus, we hypothesize an amplifying loop among lipogenesis, palmitate, Nrf2 and Nlrp3 that leads to a higher risk of NAFLD progression to NASH in a high-fructose diet compared to a high-saturated fat intake.
We found that KCs and NLRP3 play pro-inflammatory roles in the progression of NASH, probably through secretions of IL-1β and IL-18 by KCs induced by PA. PA could act as a kind of damage-associated molecular patterns to elevate the messenger RNA and protein expression levels of NLRP3, ASC, and caspase-1 in KCs from WT mice.
Our results demonstrate that (1) Elovl6 is a critical modulator for atherogenic high-fat diet-induced inflammation, oxidative stress, and fibrosis in the liver; (2) Elovl6 expression is positively correlated with severity of hepatosteatosis and liver injury in NASH patients; and (3) deletion of Elovl6 reduces palmitate-induced activation of the NLR family pyrin domain-containing 3 inflammasome; this could be at least one of the underlying mechanisms by which Elovl6 modulates the progress of NASH.