D1-like receptor antagonist inhibits IL-17 expression and attenuates crescent formation in nephrotoxic serum nephritis.
OBJECTIVE
A dopamine type 1-like receptor (D1-like-R) expressed on dendritic cells was involved in Th17 cell differentiation of naive CD4(+) T cells. Thus, we treated mice with nephrotoxic serum nephritis (NTN) with a D1-like-R antagonist to test whether Th17 cells play a role in this kidney disease.


METHODS
The SCH group of nephritic mice was administered with a D1-like-R antagonist, SCH23390, from day 0 to day 13. The kidney and spleen were collected at sacrifice on day 14. Glomerular pathology and CCR6(+) cell infiltration were quantitatively evaluated. IL-4, IFN-gamma and IL-17 mRNA levels in the kidney, and IFN-gamma and IL-17 concentrations in the supernatants from splenocytes activated in vitro were measured.


RESULTS
Crescent formation had significantly developed in the positive control (PC) group of untreated, nephritic mice, which was suppressed in the SCH group. Glomerular infiltration of CCR6(+) cells was also noted in the PC group, which was abolished in the SCH group. Renal IL-17 and IFN-gamma mRNA levels were significantly reduced in the SCH group compared with the PC group. Additionally, in vitro activation augmented IFN-gamma induction, but suppressed IL-17 induction by splenocytes from the SCH group compared with those from the PC group.


CONCLUSIONS
We identified treatment with a D1-like-R antagonist inhibited IL-17 expression and attenuated crescent formation in NTN mice.
Okada
Hirokazu
H
Department of Nephrology, Faculty of Medicine, Saitama Medical University, Saitama, Japan. hirookda@saitama-med.ac.jp
Inoue
Tsutomu
T
Hashimoto
Kumiko
K
Suzuki
Hiromichi
H
Matsushita
Sho
S
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D020381:Interleukin-17 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D009393:Nephritis / Q000276:immunology* / Q000473:pathology*; D044967:Serum
D001552:Benzazepines; D020381:Interleukin-17; C534628:SCH 23390