Parathyroid hormone induces hepatic production of bioactive interleukin-6 and its soluble receptor.

Abstract

Interleukin-6 (IL-6) is an important mediator of parathyroid hormone (PTH)-induced bone resorption. Serum levels of IL-6 and its soluble receptor (IL-6sR) are regulated in part by PTH. The PTH/PTH-related protein type 1 receptor is highly expressed in the liver, and in the current study we investigated whether the liver produces IL-6 or IL-6sR in response to PTH. Perfusion of the isolated rat liver with PTH-(1-84) stimulated rapid, dose-dependent production of bioactive IL-6 and the IL-6sR. These effects were observed at near physiological concentrations of the hormone such that 1 pM PTH induced hepatic IL-6 production at a rate of approximately 0.6 ng/min. In vitro, hepatocytes, hepatic endothelial cells, and Kupffer cells, but not hepatic stellate cells, were each found to produce both IL-6 and IL-6sR in response to higher (10 nM) concentrations of PTH. Our data suggest that hepatic-derived IL-6 and IL-6sR contribute to the increase in circulating levels of these cytokines induced by PTH in vivo and raise the possibility that PTH-induced, liver-derived IL-6 may exert endocrine effects on tissues such as bone.

• Authors: M A Mitnick, A Grey, U Masiukiewicz, M Bartkiewicz, L Rios-Velez, S Friedman, L Xu, M C Horowitz, K Insogna
• Journal: American journal of physiology. Endocrinology and metabolism (Am J Physiol Endocrinol Metab) Vol. 280 Issue 3 Pg. E405-12 (Mar 2001) ISSN: 0193-1849 [Print] United States
• PMID: 11171594 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Interleukin-6
• Parathyroid Hormone
• Peptide Fragments
• RNA, Messenger
• Receptors, Interleukin-6

Topics

• Animals
• Cell Division
• Cells, Cultured
• Endothelium, Vascular (drug effects, metabolism)
• Hepatocytes (chemistry, drug effects, metabolism)
• Humans
• Interleukin-6 (biosynthesis, genetics, pharmacology)
• Kupffer Cells (drug effects, metabolism)
• Liver (drug effects, metabolism)
• Male
• Parathyroid Hormone (pharmacology)
• Peptide Fragments (pharmacology)
• RNA, Messenger (analysis)
• Rats
• Rats, Sprague-Dawley
• Receptors, Interleukin-6 (biosynthesis)