The interaction of inflammasomes and gut microbiota: novel therapeutic insights.

Inflammasomes are complex platforms for the cleavage and release of inactivated IL-1ß and IL-18 cytokines that trigger inflammatory responses against damage-associated molecular patterns (DAMPs) or pathogen-associated molecular patterns (PAMPs). Gut microbiota plays a pivotal role in maintaining gut homeostasis. Inflammasome activation needs to be tightly regulated to limit aberrant activation and bystander damage to the host cells. Several types of inflammasomes, including Node-like receptor protein family (e.g., NLRP1, NLRP3, NLRP6, NLRP12, NLRC4), PYHIN family, and pyrin inflammasomes, interact with gut microbiota to maintain gut homeostasis. This review discusses the current understanding of how inflammasomes and microbiota interact, and how this interaction impacts human health. Additionally, we introduce novel biologics and antagonists, such as inhibitors of IL-1ß and inflammasomes, as therapeutic strategies for treating gastrointestinal disorders when inflammasomes are dysregulated or the composition of gut microbiota changes.

Oxidized low-density lipoprotein is associated with viral load and disease activity in patients with chronic hepatitis C.

BACKGROUND: The mechanisms of liver injury in chronic hepatitis C virus (HCV) infection are poorly understood. Recent evidence suggests that oxidative stress and lipid-peroxidation play a major role. The purpose of this study was to determine the serum level of oxidized low-density lipoprotein (ox-LDL), and evaluate its association with different clinically valuable parameters of liver disease in patients with chronic hepatitis C. METHODS: Forty-five untreated chronic hepatitis C patients and 45 healthy adult volunteers, matched for age, sex and BMI, were enrolled. Blood samples were collected after 12 h of fasting, and serum bilirubin, albumin, liver aminotransferases, lipid profile, prothrombin time and ox-LDL were measured. Viral load of HCV was determined in patients. Liver biopsy was performed in patients and the stage of fibrosis and grade of necroinflammatory activity were determined. Healthy controls did not undergo liver biopsy. RESULTS: Ox-LDL was significantly higher in HCV patients (42.54 ± 3.82 vs. 30.98 ± 1.66 µ/l, P < 0.01). Ox-LDL was significantly correlated to viral load (r = 0.457, P < 0.01), and grade of inflammation (r = 0.293, P < 0.05) in HCV patients. Ox-LDL was significantly higher in cirrhotic vs. noncirrhotic patients. No significant association was found between ox-LDL and Child-Pugh classification, serum albumin, liver enzymes, or prothrombin time. CONCLUSION: This study provided new data from an in vivo setting which suggests the contribution of ox-LDL to HCV pathogenesis. Our results encourage further clinical studies to evaluate the potential diagnostic and therapeutic implications of ox-LDL in HCV patients.