All-trans-retinoic acid inhibits the development of mesangial proliferative glomerulonephritis in interleukin-6 transgenic mice.
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.
Shima
Yoshihito
Y
Department of Molecular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
Iwano
Masayuki
M
Yoshizaki
Kazuyuki
K
Tanaka
Toshio
T
Kawase
Ichiro
I
Nishimoto
Norihiro
N
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D018929:Cell Culture Techniques; D049109:Cell Proliferation; D050822:Cytokine Receptor gp130 / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005921:Glomerulonephritis; D006417:Hematuria; D015850:Interleukin-6 / Q000096:biosynthesis / Q000097:blood / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D011507:Proteinuria; D051381:Rats; D019947:Receptors, Interleukin-6 / Q000096:biosynthesis* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014212:Tretinoin / Q000494:pharmacology*
D000970:Antineoplastic Agents; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D050822:Cytokine Receptor gp130; D014212:Tretinoin