TNF-α and IL-6 signals from the bone marrow derived cells are necessary for normal murine liver regeneration

• Published in: Biochimica et biophysica acta 2008-11, Vol.1782 (11), p.671-679
• Main Authors: Sudo, Kaori, Yamada, Yasuhiro, Saito, Kuniaki, Shimizu, Syogo, Ohashi, Hazuki, Kato, Tomohiro, Moriwaki, Hisataka, Ito, Hiroyasu, Seishima, Mitsuru
• Format: Article
• Language: English
• Subjects: Animals; Bone Marrow Cells - cytology; Bone Marrow Cells - physiology; Bone Marrow Transplantation; Hepatectomy; In Situ Nick-End Labeling; Interleukin-6; Interleukin-6 - genetics; Interleukin-6 - metabolism; Liver - cytology; Liver - metabolism; Liver regeneration; Liver Regeneration - physiology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; NF-kappa B - metabolism; Signal Transduction - physiology; STAT3 Transcription Factor - metabolism; Tumor necrosis factor; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0925-4439; 0006-3002; 1879-260X
• DOI: 10.1016/j.bbadis.2008.09.010

In the present study, we used bone marrow transplanted mice and revealed the role of bone marrow derived cells in liver regeneration after partial hepatectomy (PH). Irradiated wild type (WT) mice received a bone marrow transplant from either WT, TNF (tumor necrosis factor)-α knockout (KO), or interleukin (IL)-6 KO donors. Both TNF-α KO- and IL-6 KO-transplanted mice compared with WT-transplanted mice showed decreased hepatocyte DNA synthesis after PH. TNF-α KO-transplanted mice showed no nuclear factor kappa B (NF-κB) and signal transducer and activator of transcription (STAT) 3 binding after PH, while IL-6 KO-transplanted mice showed NF-κB, but not STAT3, binding. Lack of AP-1 or C/EBP binding or expression of c- jun or c-myc mRNA after PH was unrelated to the timing and amount of DNA replication. In conclusion, The TNF-α and IL-6 signals from the blood are necessary for liver regeneration and NF-κB and STAT3 binding are activated via TNF-α and IL-6 signal pathways.