Asset Details
Do you wish to reserve the book?
IL-1 receptor antagonist ameliorates inflammasome-dependent alcoholic steatohepatitis in mice
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
IL-1 receptor antagonist ameliorates inflammasome-dependent alcoholic steatohepatitis in mice
Do you wish to request the book?
IL-1 receptor antagonist ameliorates inflammasome-dependent alcoholic steatohepatitis in mice
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
IL-1 receptor antagonist ameliorates inflammasome-dependent alcoholic steatohepatitis in mice
2012
Overview
Alcoholic liver disease (ALD) is characterized by steatosis and upregulation of proinflammatory cytokines, including IL-1β. IL-1β, type I IL-1 receptor (IL-1R1), and IL-1 receptor antagonist (IL-1Ra) are all important regulators of the IL-1 signaling complex, which plays a role in inflammation. Furthermore, IL-1β maturation is dependent on caspase-1 (Casp-1). Using IL-1Ra-treated mice as well as 3 mouse models deficient in regulators of IL-1β activation (Casp-1 and ASC) or signaling (IL-1R1), we found that IL-1β signaling is required for the development of alcohol-induced liver steatosis, inflammation, and injury. Increased IL-1β was due to upregulation of Casp-1 activity and inflammasome activation. The pathogenic role of IL-1 signaling in ALD was attributable to the activation of the inflammasome in BM-derived Kupffer cells. Importantly, in vivo intervention with a recombinant IL-1Ra blocked IL-1 signaling and markedly attenuated alcohol-induced liver inflammation, steatosis, and damage. Furthermore, physiological doses of IL-1β induced steatosis, increased the inflammatory and prosteatotic chemokine MCP-1 in hepatocytes, and augmented TLR4-dependent upregulation of inflammatory signaling in macrophages. In conclusion, we demonstrated that Casp-1-dependent upregulation of IL-1β and signaling mediated by IL-1R1 are crucial in ALD pathogenesis. Our findings suggest a potential role of IL-1R1 inhibition in the treatment of ALD.
Publisher
American Society for Clinical Investigation
Subject
/ Animals
/ Carrier Proteins - biosynthesis
/ Chemokine CCL2 - biosynthesis
/ Drug Evaluation, Preclinical
/ Fatty Liver, Alcoholic - drug therapy
/ Fatty Liver, Alcoholic - etiology
/ Female
/ Interleukin 1 Receptor Antagonist Protein - therapeutic use
/ Interleukin-1alpha - biosynthesis
/ Interleukin-1beta - biosynthesis
/ Interleukin-1beta - physiology
/ Interleukin-1beta - toxicity
/ Liver Cirrhosis - prevention & control
/ Mice
/ NLR Family, Pyrin Domain-Containing 3 Protein
/ Receptors, Interleukin-1 Type I - deficiency
/ Receptors, Interleukin-1 Type I - physiology
/ Recombinant Proteins - therapeutic use
/ Signal Transduction - drug effects
