Anti-inflammatory cytokines hepatocyte growth factor and interleukin-11 are over-expressed in Polycythemia vera and contribute to the growth of clonal erythroblasts independently of JAK2V617F

Oncogene ◽  
2010 ◽  
Vol 30 (8) ◽  
pp. 990-1001 ◽  
Author(s):  
M Boissinot ◽  
C Cleyrat ◽  
M Vilaine ◽  
Y Jacques ◽  
I Corre ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Polycythemia Vera ◽  
Inflammatory Cytokines ◽  
Anti Inflammatory ◽  
Hepatocyte Growth ◽  
Interleukin 11

Up-Regulation of Anti-Inflammatory, STAT3-Activating Hepatocyte Growth Factor and Interleukin-11 In Polycythemia Vera Is Independent of JAK2V617F and Contributes to the Growth of Clonal Erythroblasts

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 796-796
Author(s):  
Marjorie Boissinot ◽  
Cedric Cleyrat ◽  
Mathias Vilaine ◽  
Yannick Jacques ◽  
Isabelle Corre ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Polycythemia Vera ◽  
Neutralizing Antibodies ◽  
Conflicts Of Interest ◽  
Mrna Levels ◽  
Hel Cells ◽  
Anti Inflammatory ◽  
Hepatocyte Growth ◽  
Interleukin 11

Abstract Abstract 796 Context: The V617F activating mutation of JAK2, JAK2V617F, characterizes Polycythemia vera (PV). However, expression of JAK2V617F does not always result in clone expansion, implying that additional events are required for the growth of JAK2-mutated progenitors and development of the PV phenotype. In the present study, we provide evidence that anti-inflammatory cytokines are required for the growth of JAK2V617F-mutated erythroid progenitors. Methods: We searched for cytokines over-expressed in PV using cytokine antibody arrays and ELISAs for analyses of serum and bone marrow (BM) plasma, and quantitative RT-PCRs for analyses of cells purified from PV patients and controls. Transient transfection of JAK2V617F and invalidation of JAK2V617F with siRNA were used to study the effect of JAK2V617F on cytokine expression. Results: We found that PV patients over-expressed anti-inflammatory hepatocyte growth factor (HGF) and interleukin-11 (IL-11), BM stromal cells (BMSC) and erythroblasts being the main producers. HGF induced the production of IL-11 and both cytokines activate the STAT3 pathway. We used neutralizing antibodies specific for IL-11 or c-MET, the HGF receptor, to block autocrine/paracrine cytokine stimulation of erythroblasts in in vitro cultures. The growth of JAK2V617F-mutated PV erythroblasts and HEL cells was inhibited by at least 40%, indicating that JAK2V617F-mutated cells depend on HGF and IL-11 for their growth. Consistent with activation of HGF/IL-11 pathways, mRNA levels of gp130 (the receptor chain responsible for signalling common to cytokines of the IL-11/IL-6 family) and STAT3 were significantly elevated in PV erythroblasts. Moreover, mRNA levels of c-MET, HGF and IL-11 were correlated, a logical finding as c-MET, HGF and IL-11 act in cascade. No correlation was found with JAK2V617F mRNA levels. To the opposite, we provide evidence that the up-regulation of HGF and IL-11 in PV is not a consequence of JAK2V617F: transient expression of JAK2V617F in BaF-3/Epo-R cells and invalidation of JAK2V617F in HEL cells using anti-JAK2 siRNA had no effect on HGF and IL-11 expression. Conclusion: Anti-inflammatory, STAT3-activating HGF and IL-11 are up-regulated in PV independently of JAK2V617F. Both cytokines contribute to the proliferation of JAK2V617F-mutated erythroblasts, suggesting that drugs blocking the HGF/IL-11 pathways, such as c-MET antagonists, could be of interest as an additional therapeutic option in PV. Marjorie Boissinot and Cedric Cleyrat contibuted equally. Disclosures: No relevant conflicts of interest to declare.

Hepatocyte Growth Factor (HGF) Induces Interleukin-11 Secretion From Osteoblasts: A Possible Role for HGF in Myeloma-Associated Osteolytic Bone Disease

Blood ◽  
1999 ◽  
Vol 94 (11) ◽  
pp. 3883-3888 ◽  
Author(s):  
Øyvind Hjertner ◽  
Maria Lyngaas Torgersen ◽  
Carina Seidel ◽  
Henrik Hjorth-Hansen ◽  
Anders Waage ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Cell Line ◽  
Bone Disease ◽  
Myeloma Cell ◽  
Physical Contact ◽  
Myeloma Cell Line ◽  
Myeloma Cells ◽  
Hepatocyte Growth ◽  
Interleukin 11

Multiple myeloma is associated with unbalanced bone remodeling causing lytic bone lesions. Interleukin-11 (IL-11) promotes osteoclast formation and inhibits osteoblast activity and may, thus, be one factor involved in cancer-induced bone destruction. We have previously shown that myeloma cells produce hepatocyte growth factor (HGF). We now report that HGF induces IL-11 secretion from human osteoblast-like cells and from the osteosarcoma cell lines Saos-2 and HOS. In coculture experiments, both the myeloma cell line JJN-3 and primary myeloma cells from 3 patients induced IL-11 secretion from osteoblasts, whereas no induction was observed with the non-HGF producing myeloma cell line OH-2. Enhanced IL-11 induction was observed with physical contact between osteoblasts and myeloma cells as compared with experiments in which contact was prohibited by tissue inserts. Anti-HGF serum strongly reduced the myeloma cell-induced IL-11 secretion. Furthermore, we show that JJN-3 cells express HGF on the cell-surface. Removal of surface-bound HGF on JJN-3 cells reduced IL-11 production induced in cocultures. Transforming growth factor β1 and IL-1 potentiated the effect of HGF on IL-11 secretion, whereas an additive effect was observed with tumor necrosis factor. Thus, myeloma-derived HGF can influence the bone marrow environment both as a soluble and a surface-bound factor. Furthermore, HGF emerges as a possible factor involved in myeloma bone disease by its ability to induce IL-11.

scholarly journals Hepatocyte Growth Factor Exerts Its Anti-Inflammatory Action by Disrupting Nuclear Factor-κB Signaling

2008 ◽  
Vol 173 (1) ◽  
pp. 30-41 ◽  
Author(s):  
Myrto Giannopoulou ◽  
Chunsun Dai ◽  
Xiaoyue Tan ◽  
Xiaoyan Wen ◽  
George K. Michalopoulos ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Anti Inflammatory ◽  
Hepatocyte Growth ◽  
Inflammatory Action

scholarly journals Anti-inflammatory activities of hepatocyte growth factor in post-ischemic heart failure

2018 ◽  
Vol 39 (10) ◽  
pp. 1613-1621 ◽  
Author(s):  
Shu-ling Rong ◽  
Xiao-lin Wang ◽  
Yi-cheng Wang ◽  
Huan Wu ◽  
Xue-dong Zhou ◽  
...  
Keyword(s):  
Heart Failure ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Ischemic Heart ◽  
Ischemic Heart Failure ◽  
Anti Inflammatory ◽  
Hepatocyte Growth

Interaction of Hepatocyte Growth Factor and Non-Steroidal Anti-Inflammatory Drugs during Gastric Epithelial Wound Healing

Digestion ◽  
2003 ◽  
Vol 67 (3) ◽  
pp. 118-128 ◽  
Author(s):  
Peter Netzer ◽  
Fred Halter ◽  
Thomas Y. Ma ◽  
Neil Hoa ◽  
Nathan Nguyen ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Epithelial Wound Healing ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Hepatocyte Growth
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