Deletion of interleukin-6 in monocytes/macrophages suppresses the initiation of hepatocellular carcinoma in mice
Hepatocellular carcinoma (HCC) is associated with inflammation, and roughly 30 % of the global population shows serological evidence of current or past infection with hepatitis B or hepatitis C virus. Resident hepatic macrophages, known as Kupffer cells (KCs), are considered as the specific tumor-as...
Gespeichert in:
Veröffentlicht in: | Journal of experimental & clinical cancer research 2016-09, Vol.35 (1), p.131, Article 131 |
---|---|
Hauptverfasser: | , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | Hepatocellular carcinoma (HCC) is associated with inflammation, and roughly 30 % of the global population shows serological evidence of current or past infection with hepatitis B or hepatitis C virus. Resident hepatic macrophages, known as Kupffer cells (KCs), are considered as the specific tumor-associated macrophages (TAMs) of HCC, and can produce various cytokines-most importantly interleukin (IL)-6-to promote tumorigenesis of HCC. However, the roles of KCs and IL-6 in carcinogenesis in the liver are still unclear.
We analyzed leukocyte-related peripheral blood data of 192 patients and constructed a mouse model in which the bone marrow was cleared out by irradiation and reconstructed using bone marrow donated from IL-6-deficient mice to further elucidate the hepatic pathological changes in response to toxic challenge and oncogenic gene mutation.
Peripheral monocyte counts and serum IL-6 levels were significantly higher in patients with HCC than in those without HCC. In addition, there was a significant difference in the levels of IL-6 among individuals with different histopathological grades. In mice with selective IL-6 ablation in monocytes/KCs, we observed decreased toxic liver injury, inflammatory infiltration, and systemic inflammation. In Mdr2-deficient mice, which spontaneously developed HCC, the loss of IL-6 in monocytes/KCs resulted in inhibition of IL-6/signal transducer and activator of transcription 3 signaling, decreased serum IL-6 levels, and delayed tumorigenesis.
Our findings demonstrate that increased TAM-derived IL-6 had an amplifying effect on the inflammation response, thereby promoting the occurrence and development of HCC. |
---|---|
ISSN: | 1756-9966 0392-9078 1756-9966 |
DOI: | 10.1186/s13046-016-0412-1 |