Curcumin Elevates microRNA‐183‐5p via Cathepsin B‐Mediated Phosphatidylinositol 3‐Kinase/AKT Pathway to Strengthen Lipopolysaccharide‐Stimulated Immune Function of Sepsis Mice

Abstract

Curcumin (Cur), a natural polyphenol compound, has been testified to modulate innate immune responses and also showed anti-inflammatory properties. Nevertheless, the mechanism was still poorly unknown, especially regarding Cur-modulated microRNAs (miRNAs) under the inflammatory response. CD39+ regulatory T cells (Tregs) were provided with distinct immunosuppressive action and exerted a critical role in the modulation of immune balance in sepsis. Nevertheless, the impact of Cur on the immune function of sepsis mice has not been reported. In this study, the influence of Cur on the inflammatory response and immune function of sepsis mice via augment of miR-183-5p and Cathepsin B (CTSB)-mediated phosphatidylinositol 3-kinase (PI3K)/AKT pathway was explored. Adoption of 20 mg/kg Cur was for gavage. In the meantime, injection of plasmid vectors of interference with miR-183-5p or CTSB was into the tail vein. Intraperitoneal injection of lipopolysaccharide (10 mg/kg) was to stimulate model of sepsis mice. Histopathological changes of sepsis mice were observed. The contents of tumor necrosis factor-α and Interleukin (IL)-1β and IL-6 in serum of mice were examined. Detection of alanine aminotransferase, aspartate aminotransferase (AST), urea nitrogen (BUN), and creatinine in serum of mice was performed. Test of the percentage of CD39+ Tregs in tail venous blood of mice was implemented. Examination of miR-183-5p, CTSB, and PI3K/AKT was performed. The targeting of miR-183-5p and CTSB was detected. Cur was available to ameliorate the histological damage, to reduce the content of inflammatory factors, AST, and BUN, and to decline the percentage of CD39+ Tregs in tail venous blood of sepsis mice. Elevated miR-183-5p or silenced CTSB was available to further enhance the protection of Cur. Cur was available to accelerate miR-183-5p, which negatively modulated CTSB and Cur-mediated PI3K/AKT pathway via the miR-183-5p/CTSB axis to restrain inflammation of sepsis mice and enhance its immune function.

The Impact of Curcumin on Immune Response: An Immunomodulatory Strategy to Treat Sepsis

“…Curcumin might function by regulating miRNA expression in the inflammatory response [ 102 ]. One study investigated the effects of curcumin on the immune response of infected animals through the increase in the miRNA-183-5p- and Cathepsin B (CTSB)-mediated phosphatidylinositol 3-kinase (PI3K)/AKT pathway [ 103 ]. Curcumin was administered for forced feeding, and i.v.…”

“…Curcumin administration reduced tissue injury, decreased the number of inflammatory elements, and reduced the frequency of CD39 + Tregs in the venous blood of sepsis animals. Curcumin accelerated miRNA-183-5p, which negatively regulated CTSB and the curcumin-mediated PI3K/AKT pathway through the miRNA-183-5p/CTSB axis in order to limit inflammation and increase its immune activity [ 103 ] ( Figure 2 ).…”