ABSTRACT
Objective:To investigate the role and mechanism of exogenous derivative 4-octyl itaconate (4-OI) in lipopolysaccharide (LPS)-induced acute lung injury (ALI).Methods:C57BL/6 male mice were randomly divided into the control group, 4-OI group, LPS group, 4-OI+LPS group and deferiprone (DFP)+LPS group, with 6 mice in each group. LPS-induced ALI model was established by intraperitoneal injection of LPS. For the 4-OI+LPS group, mice were pretreated with 4-OI for 2 h before stimulation with LPS. The mice were sacrificed 12 h later and lung tissues were collected for pathological and molecular biological examination. Hematoxylin-eosin and Masson staining were used to detect the level of lung injury and collagen deposition. The expression levels of inflammatory cytokines and ferroptosis associated genes were detected by real-time quantitative PCR, and ferroptosis associated proteins were detected by Western blotting. The chi-square test was performed before the measurement data were counted. One-way analysis of variance was used to compare differences between multiple groups.Results:Compared with the control group, the histopathological damage was aggravated, and collagen deposition and lung injury score and lung wet-dry ratio were significantly increased in the LPS group (all P<0.05), and 4-OI pre-treatment significantly alleviated LPS-induced ALI. 4-OI treatment also significantly reduced the mRNA level of inflammatory cytokines, including IL-1β [(4.38±0.47) vs. (32.65±4.49)], IL-6 [(3.97±0.64) vs. (12.22±0.91)] and TNF-α [(15.06±2.26) vs. (38.53±2.31)]. At the same time, compared with the control group, the levels of lipid peroxidation metabolite 4-hydroxynonenal and malondialdehyde, iron level of lung tissue were significantly increased in the LPS group, and the mRNA level of ferroptosis marker prostaglandin-endoperoxide synthase 2 was also significantly increased (all P<0.05), but these indicators were significantly lower in the 4-OI+LPS group than in the LPS group. The results of immunofluorescence, Western blotting and PCR showed that the protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione peroxidase 4 (GPX4) and ferritin heavy chain (FTH1) significantly decreased in the LPS group, while 4-OI treatment significantly increased the Nrf2, GPX4 and FTH1 levels, and showed similar inhibition of ferroptosis with DFP (all P<0.05). Conclusions:4-OI attenuates LPS-induced ALI by increasing Nrf2 and upregulating FTH1 and GPX4, providing a potential drug and its theoretical mechanism for the prevention and treatment of ALI.
ABSTRACT
With the maturity of surgical techniques, the success rate of liver transplantation has been gradually increased. However, the establishment of long-term immune tolerance after operation still faces multiple challenges. Kupffer cells are tissue-resident macrophages, which could reside in the liver and polarize into different directions following liver transplantation, forming M1 Kupffer cells and M2 Kupffer cells. M1 Kupffer cells have pro-inflammatory function, whereas M2 Kupffer cells possess immunoregulatory function. It contributes to the establishment of immune tolerance by inhibiting the quantity and function of M1 Kupffer cells, or enhancing the quantity and function of M2 Kupffer cells. The polarization of Kupffer cells is regulated by many cytokines and signals, which provides an opportunity for therapies to establish immune tolerance of liver transplantation by interfering Kupffer polarization. In this article, the relationship between Kupffer cell polarization and immune tolerance of liver transplantation, and the mechanism of Kupffer cell polarization were reviewed, aiming to provide reference for establishing immune tolerance of liver transplantation.
ABSTRACT
This paper described the treatment of itaconic acid strain of Aspergillus terreus As 3 2811 with uv irradiation and high temperature The mutant was obtained which grew in culture media containing succinic acid as the only carbon source Its productivity of itaconic acid was 5 times higher than the original strain The producing acid conditions were optimized by orthogonal experimental design By batch feeding glucose fermentation ,the itoconic acid productivity could be improved by 39 92%