Interleukin-6 stimulates tubular regeneration in rats with glycerol-induced acute renal failure.
Interleukin-6 stimulates tubular regeneration in rats with glycerol-induced acute renal failure.


BACKGROUND
Interleukin 6 (IL-6) is a pleiotropic cytokine released after endotoxemia, trauma and organ injury. IL-6 may act in cellular proliferation activating transduction signals and Ras/Map cascade or the HGF/c-met axis. We tested the effect of IL-6 in the regeneration of tubular epithelia after acute tubular necrosis (ATN) in rats.


METHODS
Rats with glycerol-induced acute renal failure (Gly-ARF) were treated with IL-6 200 microg/kg/day. Functional, histological and immunohistochemical tests were done 24 and 72 h after Gly-ARF to localise mitotic cells (BrdU). The renal expression of c-met (Western-Blot) and circulating levels of HGF (ELISA) were also determined.


RESULTS
Rats with Gly-ARF had reduced creatinine clearance that was not influenced by IL-6. The histological appearance of ATN was also unaffected by IL-6. The IL-6 treated rats showed a significant increase in tubular cell proliferation in cortex and medulla, as well as in the expression of c-met protein in the renal cortex, compared to untreated Gly-ARF rats. The plasma HGF concentration was equally elevated in treated and untreated Gly-ARF rats.


CONCLUSIONS
IL-6 stimulates tubular regeneration after Gly-ARF and increases the expression of c-met in the renal cortex. Gly-ARF rats have high circulating levels of HGF that is targeted to act in the injured kidneys by the IL-6 overexpressed renal c-met.
Homsi
Eduardo
E
Division of Nephrology, Faculty of Medical Sciences, State University of Campinas, Campinas, São Paulo, Brasil. ehomsi@netway.com.br
Ribeiro-Alves
Maria A
MA
Lopes de Faria
José B
JB
Dias
Eliana P O
EP
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D005990:Glycerol; D017228:Hepatocyte Growth Factor / Q000097:blood; D015850:Interleukin-6 / Q000494:pharmacology*; D007683:Kidney Tubular Necrosis, Acute / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D007684:Kidney Tubules / Q000737:chemistry / Q000473:pathology / Q000502:physiology*; D008297:Male; D019859:Proto-Oncogene Proteins c-met / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration / Q000187:drug effects*; D014556:Urine
D015850:Interleukin-6; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D005990:Glycerol