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Updated: Jul 2, 2026

Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells
Published on: May 22, 2014
The inhibitory effect of interleukin 1beta on rat hepatocyte DNA synthesis is mediated by nitric oxide
1Thomas E. Starzl Transplant Institute, Department of Surgery, University of Pittsburgh School of Medicine, PA 15213, USA.
Abstract:
Interleukin 1beta (IL-1beta) and nitric oxide (NO) have potent growth-regulatory effects on different cell types. We found that epidermal growth factor-induced DNA synthesis in primary cultures of adult rat hepatocytes was inhibited by NO when it was provided by addition to the cultures of S-nitroso-N-acetyl-penicillamine (SNAP), an NO donor, as well as by addition of IL-1beta in a dose-dependent manner. IL-1beta also induced NO production and inducible NO synthase (iNOS) gene expression. The inhibition of DNA synthesis by IL-1beta was completely abrogated when NO production was inhibited by N-monomethyl-L-arginine (NMA), a competitive inhibitor of iNOS. IL-1beta-receptor antagonist (IL-1ra), which interferes with the interaction of IL-1beta with target cells, also abolished the inhibitory effects of IL-1beta on hepatocyte DNA synthesis as well as IL-1beta-induced iNOS gene expression. We also found that hepatocyte DNA synthesis inhibition by IL-1beta was completely antagonized by providing deoxynucleosides to bypass the block in ribonucleotide reductase, a rate-limiting step in DNA synthesis, thus implicating this enzyme in the mechanism of growth inhibition by IL-1beta. These experiments extended prior observations on the growth-inhibitory actions of IL-1beta on hepatocyte DNA synthesis, involving the IL-1beta receptor, NO production, and ribonucleotide reductase.
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