All-trans-retinoic acid inhibits the development of mesangial proliferative glomerulonephritis in interleukin-6 transgenic mice.

Abstract

All-trans-retinoic acid (ATRA), a vitamin A derivative, was reported to suppress the interleukin-6 (IL-6) production and to downregulate the IL-6 receptor (IL-6R) and/or its signal transducer glycoprotein 130. We investigated the in vivo antinephritic effect of ATRA on IL-6 transgenic mice which had developed mesangial proliferative glomerulonephritis (PGN) as well as its in vitro inhibitory effect on the proliferation of rat mesangial cells. In vivo experiments on IL-6 transgenic mice showed that ATRA administration suppressed proteinuria and hematuria and reduced the IL-6 concentrations; furthermore, histological examination demonstrated that it improved PGN. In vitro experiments using rat mesangial cells demonstrated that ATRA inhibited cell growth in a dose-dependent manner within a range from 10(-4) to 10(-6) M. This inhibition by ATRA was partially counteracted by the addition of IL-6. RT-PCR assay results showed that ATRA also reduced IL-6R, but not the glycoprotein 130 expression in mesangial cells. These findings indicate that, by blocking of the IL-6 function, ATRA may be therapeutically effective in PGN.

• Authors: Yoshihito Shima, Masayuki Iwano, Kazuyuki Yoshizaki, Toshio Tanaka, Ichiro Kawase, Norihiro Nishimoto
• Journal: Nephron. Experimental nephrology (Nephron Exp Nephrol) Vol. 100 Issue 1 Pg. e54-62 ( 2005) ISSN: 1660-2129 [Electronic] Switzerland
• PMID: 15795517 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Interleukin-6
• Receptors, Interleukin-6
• Cytokine Receptor gp130
• Tretinoin

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Cell Culture Techniques
• Cell Proliferation
• Cytokine Receptor gp130 (biosynthesis)
• Dose-Response Relationship, Drug
• Down-Regulation
• Glomerulonephritis
• Hematuria
• Interleukin-6 (biosynthesis, blood, genetics, physiology)
• Mice
• Mice, Transgenic
• Proteinuria
• Rats
• Receptors, Interleukin-6 (biosynthesis, physiology)
• Reverse Transcriptase Polymerase Chain Reaction
• Tretinoin (pharmacology)