Hepatic haemangiomas: possible association with IL-17.
BACKGROUND
Interleukin-17 (IL-17) has been cast as a major player in angiopoiesis of carcinoma, but its role in hepatic haemangioma is not entirely clear.


OBJECTIVE
The aim of this study is to address the expression levels and the molecular mechanism underlying the role of IL-17 on hepatic haemangioma progression.


RESULTS
20 hepatic haemangioma patients and 15 healthy subjects were included in this study. IL-17 mRNA levels were examined by PCR-based methods and protein levels by western blot. We observed a significant increase in tissue IL-17 mRNA and protein levels in hepatic haemangioma compared to normal liver tissue. Matrix metalloproteinase protein levels were slightly elevated in haemangiomas compared to normal, and IL-6 and phospho-stat3 levels were markedly elevated. However, no differences in mRNA levels of angiogenesis-associated cytokines such as vascular endothelial growth factor were seen in hepatic haemangiomas compared to normal cases taken from donor livers at the time of organ harvest. IL-17 was localised to CD4-positive cells by flow cytometry and to stromal cells and endothelial cells by immunohistochemistry. Owing to the absence of an animal model of haemangioma, we examined the effects of IL-17 on angiogenesis-related functions of vascular endothelial cells in vitro. Notably, IL-17, when added to cell cultures of human umbilical cord-derived endothelial cells, had an effect on the secretion of IL-6 and p-stat3.


CONCLUSIONS
Based on these findings, we propose that IL-17 may mediate the angiogenesis in a IL-6-Stat3-dependent manner and play an important role in the pathophysiology of hepatic haemangioma.
Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, China.
ZhaoJing
Z
Wang
Yifeng
Y
Yuan
Haiwen
H
Zhuang
Runqiu
R
Jiang
Jiajie
J
Hou
Qi
Q
Chen
Feng
F
Zhang
D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism; D005434:Flow Cytometry; D006391:Hemangioma / Q000098:blood supply / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008099:Liver / Q000098:blood supply / Q000166:cytology / Q000378:metabolism; D008113:Liver Neoplasms / Q000098:blood supply / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000378:metabolism; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism
D020381:Interleukin-17; D015850:Interleukin-6; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D042442:Vascular Endothelial Growth Factors; D020780:Matrix Metalloproteinase 9