STAT3 signaling within hepatocytes is required for anemia of inflammation in vivo.
BACKGROUND
Anemia of inflammation, commonly observed in patients with chronic diseases, is associated with decreased serum iron. Hepcidin, mainly produced by hepatocytes in a STAT3- and/or SMAD-dependent manner, is involved in iron homeostasis. What remains to be established is whether or not the hepatic IL-6/STAT3 signal has a role in anemia of inflammation in vivo.


METHODS
Turpentine oil was subcutaneously injected into wild-type mice or hepatocyte-specific STAT3-deficient mice (L-STAT3KO) to induce inflammation.


RESULTS
Turpentine injection increased serum IL-6 levels. It activated liver STAT3 in wild-type mice, but not in L-STAT3KO mice. In chronic inflammation, wild-type mice showed decreased serum iron levels and anemia with up-regulation of hepcidin levels in the liver. In contrast, L-STAT3KO mice showed no increase in hepatic hepcidin levels or anemia.


CONCLUSIONS
Liver STAT3 is critically involved in the development of anemia of inflammation via the expression of hepcidin. The liver regulates anemia of inflammation through STAT3 signaling.
Sakamori
Ryotaro
R
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
Takehara
Tetsuo
T
Tatsumi
Tomohide
T
Shigekawa
Minoru
M
Hikita
Hayato
H
Hiramatsu
Naoki
N
Kanto
Tatsuya
T
Hayashi
Norio
N
D000740:Anemia / Q000209:etiology / Q000503:physiopathology*; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D022781:Hepatocytes / Q000378:metabolism; D064451:Hepcidins; D007249:Inflammation / Q000150:complications* / Q000503:physiopathology; D015850:Interleukin-6 / Q000097:blood; D007501:Iron / Q000097:blood; D008099:Liver / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014425:Turpentine / Q000633:toxicity; D015854:Up-Regulation
D023181:Antimicrobial Cationic Peptides; C579599:Hamp protein, mouse; D064451:Hepcidins; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D007501:Iron; D014425:Turpentine