Colchicine suppresses osteopontin expression and inflammatory cell infiltration in chronic cyclosporine nephrotoxicity.
BACKGROUND
Colchicine (Col) is beneficial to renal injury because of its anti-inflammatory effect, but its mechanism has yet to be elucidated. The present study was designed to evaluate the inhibitory effects of colchicine on osteopontin (OPN) expression and the macrophage accumulation in chronic cyclosporine (CsA) nephrotoxicity in rats.


METHODS
Male adult Sprague-Dawley rats on a low salt diet (LSD, 0.05% sodium) were treated daily with Col (30 microg/kg), CsA (15 mg/kg), and both CsA and colchicine or vehicle (olive oil 1 ml/kg) for 4 weeks. The effects of colchicine on chronic CsA nephrotoxicity were evaluated by examining renal function, histopathology, and ED-1 positive cells. The expressions of OPN mRNA and protein were estimated respectively by Northern blot and immunohistochemistry.


RESULTS
Compared with vehicle-treated rats, CsA-treated rats showed an increase in serum creatinine, a decline in creatinine clearance rate, and tubulointerstitial fibrosis (all p < 0.01). Concomitant administration of colchicine reversed all of the above parameters (all p < 0.01). Of note, the upregulated expression of osteopontin mRNA and protein seen in CsA-treated rats was significantly decreased after colchicine treatment. Furthermore, the expression of osteopontin mRNA was strongly correlated with the number of ED-1 positive cells (r = 0.712, p < 0.001) and the tubulointerstitial fibrosis score (r = 0.586, p = 0.007).


CONCLUSIONS
Colchicine is capable of abrogating the upregulation of chemotactic OPN expression and macrophage influx, and this is associated with improved renal tubulointerstitial fibrosis in chronic CsA nephrotoxicity.
Li
Can
C
Department of Internal Medicine, KangNam St. Mary's Hospital, Catholic University of Korea, 505 BanPo-Dong, SeoCho-Ku, 137-040 Seoul, Korea.
Yang
Chul Woo
CW
Ahn
Hee Jong
HJ
Kim
Wan Young
WY
Park
Cheol Whee
CW
Park
Joo Hyun
JH
Cha
Jung Ho
JH
Kim
Jin
J
Kim
Yong Soo
YS
Bang
Byung Kee
BK
D000818:Animals; D003078:Colchicine / Q000494:pharmacology*; D016572:Cyclosporine / Q000633:toxicity*; D005355:Fibrosis; D015870:Gene Expression / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000633:toxicity; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D007668:Kidney / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D008297:Male; D053495:Osteopontin; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012795:Sialoglycoproteins / Q000235:genetics* / Q000378:metabolism*
D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D012795:Sialoglycoproteins; C506897:Spp1 protein, rat; D053495:Osteopontin; D016572:Cyclosporine; D003078:Colchicine