Rutin modulates ASC expression in NLRP3 inflammasome: a study in alcohol and cerulein-induced rat model of pancreatitis.

Abstract

Inflammasomes are protein complexes formed in response to tissue injury and inflammation to regulate the formation of proinflammatory cytokines. Nod-like receptor pyrin domain containing 3 (NLRP3) is one such inflammasome involved in pancreatic inflammation. Caspase activation recruitment domain (CARD) is an interaction motif found in all the major components of NLRP3 inflammasome such as apoptosis associated speck-like CARD containing protein (ASC) and procaspase-1. NLRP3 activates procaspase-1 with the concerted action of CARD domain of ASC. In the present study, the effect of rutin, a natural flavonoid on the expression of ASC of NLRP3, was investigated in rats treated with ethanol (EtOH) and cerulein (Cer). Male albino Wistar rats were divided into four groups. Groups 1 and 2 rats were fed normal diet, whereas groups 3 and 4 rats were fed EtOH (36 % of total calories) containing diet for a total period of 5 weeks and also administered Cer (20 µg/kg body weight i.p.) thrice weekly for the last 3 weeks. In addition, groups 2 and 4 rats received daily 100 mg/kg body weight of rutin from third week. Rutin co-administration significantly decreased the level of pancreatic marker enzymes, oxidative stress markers, inflammatory markers, mRNA expression of caspase-1, cytokines, ASC-NLRP3, and protein expression of caspase-1 and ASC in rats received EtOH-Cer. The results of the study revealed that rutin can reduce inflammation in pancreas probably by influencing the down regulation of ASC-NLRP3 which might result in the reduced activation of caspase-1 and controlled cytokine production.

• Authors: Ravikumar Aruna, Arumugam Geetha, Periyanayagam Suguna
• Journal: Molecular and cellular biochemistry (Mol Cell Biochem) Vol. 396 Issue 1-2 Pg. 269-80 (Nov 2014) ISSN: 1573-4919 [Electronic] Netherlands
• PMID: 25060908 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Antioxidants
• Apoptosis Regulatory Proteins
• Biomarkers
• CARD Signaling Adaptor Proteins
• Carrier Proteins
• Enzymes
• Inflammasomes
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, rat
• Pycard protein, rat
• Receptors, Cytoplasmic and Nuclear
• Ethanol
• Rutin
• Ceruletide
• Caspase 1
• Glutathione

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Antioxidants (metabolism)
• Apoptosis Regulatory Proteins (genetics, metabolism)
• Biomarkers (metabolism)
• CARD Signaling Adaptor Proteins
• Carrier Proteins
• Caspase 1 (genetics, metabolism)
• Ceruletide (toxicity)
• Disease Models, Animal
• Enzymes (metabolism)
• Ethanol (toxicity)
• Glutathione (metabolism)
• Inflammasomes (drug effects, metabolism)
• Male
• NLR Family, Pyrin Domain-Containing 3 Protein
• Oxidative Stress (drug effects)
• Pancreatitis (chemically induced, drug therapy, metabolism)
• Rats, Wistar
• Receptors, Cytoplasmic and Nuclear (genetics, metabolism)
• Rutin (pharmacology)