Inhibiting CD44-ICD Attenuates LPS-Induced Initiation of Hepatic Inflammation in Septic Mice.

Sepsis is a severe condition induced by microbial infection. It elicits a systemic inflammatory response, leading to multi-organ failure, and the liver, as a scavenger, plays a significant role in this process. Controlling hepatic inflammation and maintaining liver function is crucial in managing sepsis. CD44-ICD, as a CD44 signal transductor, is involved in multiple inflammatory responses. However, the role of CD44-ICD in lipopolysaccharide (LPS)-induced hepatic inflammation has not been investigated. Therefore, we aimed to examine whether CD44-ICD initiates hepatic inflammation in septic mice. We induced hepatic inflammation in mice by administering LPS. DAPT, a CD44-ICD inhibitor, was given to mice or Chang cells 30 min or 1 h before LPS administration (10 mg/kg, i.p., or 100 ng/mL, respectively). Inhibition of CD44-ICD decreased the level of aspartate aminotransferase (AST), alanine aminotransferase (ALT), hepatic necrosis, inflammatory cell infiltration, interleukin (IL)-1ß, inducible NO synthase (iNOS), nitric oxide (NO) production, nuclear factor (NF)κB signaling pathway proteins, and CD44 expression in mice. CD44-ICD inhibition also decreased IL-1ß and CD44 expression levels in Chang cells. CD44-ICD may be a primary regulatory function in CD44-associated LPS-induced initiation of hepatic inflammation in mice.

Attenuation of inflammatory response in the EAE model by PEGlated nanoliposome of pistachio oils.

The aim of this study was to investigate the effect of PEGlated nanoliposome of pistachio unsaturated oils (PEGNLPUOs) to attenuate the inflammatory response in the EAE model by modulating of NFKB and oxidative stress signaling pathway. Real-time PCR demonstrated that the administration of 10%v/v PEGNLPUOs significantly decreased the expression level of AKT1, MAPK, and NFKB genes from NFKB signaling pathway and MGST1, NOS2, and HO-1 genes from oxidative stress signaling pathway. This study showed that the administration of pistachio oil and PEGNLPUOs at a concentration of 10%v/v decreased the number and percentage of Th1(CD4+) and increased Th2(CD8+) cells.

Anaphylatoxin C5a induces inflammation and reduces insulin sensitivity by activating TLR4/NF-kB/PI3K signaling pathway in 3T3-L1 adipocytes.

Obesity closely correlates with metaflammation and characterizes with systemic-chronic-low inflammation. This study aims to evaluate effects of C5a on the inflammatory response and insulin resistance in 3T3-L1 adipocytes. 3T3-L1 pre-adipocytes were induced to the mature 3T3-L1 adipocytes. Then, 3T3-L1 were intervened with anaphylatoxin C5a, lipopolysaccharide (LPS) and C5a + LPS, respectively. Levels of Omentin, Chemerin, Vaspin and Apelin 12 in supernatants of medium were examined using ELISA. C5L2, C5a receptor (C5aR), I kappa B (IkB), IkB kinase (IKK), insulin receptor substrate 1 (IRS-1), IRS-2, PI3 K, p-PI3 K and ß-actin were examined using RT-PCR and western blot assay, respectively. C5L2-C5aR colocalization was identified using immunofluorescence double label. NF-kB expression or activity was evaluated using electrophoretic mobility shift assay (EMSA), dual luciferase assay and immunofluorescence assay, respectively. The glucose uptake and insulin sensitivity were also evaluated. Results showed that C5a intervention significantly enhanced inflammatory molecule levels in supernatants of 3T3-L1 adipocytes. IKK inflammatory signaling pathway participated in C5a induced inflammation of 3T3-L1 adipocytes. C5a triggered the colocalization of C5L2 and C5aR and activated the NF-kB inflammatory signaling pathway. C5a intervention in 3T3-L1 adipocytes decreased the glucose uptake and resulted in reduction of insulin sensitivity. Insulin signaling pathway participated in C5a caused insulin sensitivity reduction. C5a intervention triggered the phosphorylation of PI3 K. In conclusion anaphylatoxin C5a induced inflammatory response by activating TLR4/NF-kB signaling pathway and generating C5L2-C5aR dimer, and caused insulin sensitivity reduction by activating PI3 K signaling pathway.