caa a22 4500 445882530 CHVBK 20180317145548.0 cr unu---uuuuu 170323e20110201xx s 000 0 eng 10.1007/s10157-010-0342-8 doi (NATIONALLICENCE)springer-10.1007/s10157-010-0342-8 Effects of TJN-598, a new selective phosphodiesterase type IV inhibitor on anti-Thy1 nephritis in rats [Elektronische Daten] [Chiharu Sadakane, Yoshio Kase, Junichi Koseki, Yoshihiro Hasegawa, Shoichiro Shindo, Hirobumi Maruyama, Shuichi Takeda, Hiroshi Takeda, Tomohisa Hattori] Background: Phosphodiesterase type IV (PDEIV) plays an important role in the immune response and inflammation. However, it is well known that classical PDEIV inhibitors have systemic side effects, so the clinical and chronic use of these agents as therapy for glomerulonephritis is difficult. This study was performed to elucidate the anti-nephritic effects of TJN-598, a new chemical compound derived from herbal components, on experimental mesangial proliferative glomerulonephritis. Methods: We first examined the effects of TJN-598 and captopril on mesangial expansion induced by anti-Thy1 serum in rats. Second, to investigate the effects of TJN-598 and rolipram, which are typical PDEIV inhibitors, on the production of tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β1, glomeruli were isolated from rats with anti-Thy1 nephritis and incubated with the test drugs in vitro for 48h. Results: Treatment with TJN-598 prevented an increase in the mesangial area/total glomerular area, in the number of cells in the glomerular cross section and matrix index. TJN-598 also inhibited the increases in the expression of α-smooth muscle actin, the TGF-β1-positive area, in the number of ED-1 positive cells and proliferating cell nuclear antigen-positive cells in the glomeruli. Furthermore, administration of TJN-598 inhibited increases in the levels of TGF-β1 protein derived from glomeruli with anti-Thy-1 nephritis. The addition of both TJN-598 and rolipram to the culture supernatant inhibited both increased expression of TGF-β1 and increases in levels of TNF-α in glomeruli isolated from rats with anti-Thy1 nephritis in a dose-dependent manner. Conclusion: These results suggest that TJN-598, a PDEIV inhibitor, is effective against expansion of mesangial cells, via the suppression of secretion of TGF-β1 and TNF-α from inflamed glomeruli. Japanese Society of Nephrology, 2010 Anti-Thy1 nephritis nationallicence TJN-598 nationallicence Phosphodiesterase nationallicence Mesangium nationallicence Sadakane Chiharu Tsumura Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki, Japan aut Kase Yoshio Tsumura Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki, Japan aut Koseki Junichi Tsumura Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki, Japan aut Hasegawa Yoshihiro Tsumura Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki, Japan aut Shindo Shoichiro Tsumura Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki, Japan aut Maruyama Hirobumi Tsumura Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki, Japan aut Takeda Shuichi Tsumura Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki, Japan aut Takeda Hiroshi Division of Pharmasciences, Department of Pathophysiology and Therapeutics, Faculty of Pharmaceutical Sciences, Hokkaido University, N12 W6, Kita-ku, 060-0812, Sapporo, Japan aut Hattori Tomohisa Tsumura Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki, Japan aut Clinical and Experimental Nephrology Springer Japan 15/1(2011-02-01), 14-24 1342-1751 15:1<14 2011 15 10157 https://doi.org/10.1007/s10157-010-0342-8 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10157-010-0342-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Sadakane Chiharu Tsumura Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki, Japan aut NATIONALLICENCE 700 1- Kase Yoshio Tsumura Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki, Japan aut NATIONALLICENCE 700 1- Koseki Junichi Tsumura Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki, Japan aut NATIONALLICENCE 700 1- Hasegawa Yoshihiro Tsumura Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki, Japan aut NATIONALLICENCE 700 1- Shindo Shoichiro Tsumura Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki, Japan aut NATIONALLICENCE 700 1- Maruyama Hirobumi Tsumura Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki, Japan aut NATIONALLICENCE 700 1- Takeda Shuichi Tsumura Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki, Japan aut NATIONALLICENCE 700 1- Takeda Hiroshi Division of Pharmasciences, Department of Pathophysiology and Therapeutics, Faculty of Pharmaceutical Sciences, Hokkaido University, N12 W6, Kita-ku, 060-0812, Sapporo, Japan aut NATIONALLICENCE 700 1- Hattori Tomohisa Tsumura Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki, Japan aut NATIONALLICENCE 773 0- Clinical and Experimental Nephrology Springer Japan 15/1(2011-02-01), 14-24 1342-1751 15:1<14 2011 15 10157 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer