The inhibitory effect of interleukin 1β on rat hepatocyte DNA synthesis is mediated by nitric oxide

• DOI: 10.1002/hep.510280221
• Publication Date: 2004-07-27T23:57:44Z
• Authors: Ziqiu Wang; Meifang Wang; Brian I. Carr
• Keywords: Ribonucleotide reductase

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 provided addition to the S-nitroso-N-acetyl-penicillamine (SNAP), an donor, as well IL-1beta a dose-dependent manner. also induced production inducible synthase (iNOS) gene expression. The inhibition completely abrogated N-monomethyl-L-arginine (NMA), competitive inhibitor iNOS. IL-1beta-receptor antagonist (IL-1ra), which interferes with interaction target cells, abolished inhibitory hepatocyte IL-1beta-induced iNOS antagonized providing deoxynucleosides bypass block ribonucleotide reductase, rate-limiting step synthesis, thus implicating this enzyme mechanism IL-1beta. These experiments extended prior observations growth-inhibitory actions involving receptor, production, reductase.