In vivo effects of interleukin‐17 on haematopoietic cells and cytokine release in normal mice

Abstract

In order to gain more insight into mechanisms operating on the haematopoietic activity of the T-cell-derived cytokine, interleukin-17 (IL-17) and target cells that first respond to its action in vivo, the influence of a single intravenous injection of recombinant mouse IL-17 on bone marrow progenitors, further morphologically recognizable cells and peripheral blood cells was assessed in normal mice up to 72 h after treatment. Simultaneously, the release of IL-6, IL-10, IGF-I, IFN-gamma and NO by bone marrow cells was determined. Results showed that, in bone marrow, IL-17 did not affect granulocyte-macrophage (CFU-GM) progenitors, but induced a persistant increase in the number of morphologically recognizable proliferative granulocytes (PG) up to 48 h after treatment. The number of immature erythroid (BFU-E) progenitors was increased at 48 h, while the number of mature erythroid (CFU-E) progenitors was decreased up to 48 h. In peripheral blood, white blood cells were increased 6 h after treatment, mainly because of the increase in the number of lymphocytes. IL-17 also increased IL-6 release and NO production 6 h after administration. Additional in vitro assessment on bone marrow highly enriched Lin- progenitor cells, demonstrated a slightly enhancing effect of IL-17 on CFU-GM and no influence on BFU-E, suggesting the importance of bone marrow accessory cells and secondary induced cytokines for IL-17 mediated effects on progenitor cells. Taken together, these results demonstrate that in vivo IL-17 affects both granulocytic and erythroid lineages, with more mature haematopoietic progenitors responding first to its action. The opposite effects exerted on PG and CFU-E found at the same time indicate that IL-17, as a component of a regulatory network, is able to intervene in mechanisms that shift haematopoiesis from the erythroid to the granulocytic lineage.

Th17 and non-Th17 interleukin-17-expressing cells in chronic lymphocytic leukemia: delineation, distribution, and clinical relevance

“…Of note, we did not detect IL-17A + cells in spleens from patients with documented extramedullary hematopoiesis secondary to non-neoplastic diseases (not shown). Although the role of myeloid-derived IL-17A + cells in CLL spleens is unclear, these cells may mediate a feed-forward process, because IL-17 can promote G-CSF production resulting in granulopoiesis 19 and the spleens we found to have higher percentages of IL-17A + cells were in two patients who had received G-CSF. Although elevated levels of IL-17A are associated with autoimmune diseases, 5 only one of the CLL patients whose spleens we studied exhibited autoimmune phenomena.…”

“…[12][13][14][15] IL-17 has pro-and anti-tumor actions. 16,17 Functions of IL-17 relevant to cancer include angiogenesis, 18 granulopoiesis, 19 osteoclast induction, 20 and induction of cytokines such as IL-6, TGF-β, granulocyte colony-stimulating factor (G-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF), as well as matrix metalloproteinase and intercellular adhesion molecule-1 in a variety of cell types, including bone marrow stromal cells. 21,22 Because of its multitude of actions, the Th17/IL-17 axis may affect development of solid tumors (ovarian, lung, and liver cancers) [23][24][25] and hematologic cancers (myeloma, acute myeloid leukemia, and non-Hodgkin's lymphoma).…”

CD47 Deficiency Does Not Impede Polymorphonuclear Neutrophil Transmigration but Attenuates Granulopoiesis at the Postacute Stage of Colitis

“…Because IL-17A was reported to stimulate granulopoiesis through inducing G-CSF (13–16), we suspected that lacking IL-17A was the reason for inadequate granulopoiesis in CD47 −/− mice during colitis. As shown in Fig.…”

“…In particular, IL-17 (IL-17A/F) is suggested to induce G-CSF, which in turn promotes granulopoiesis in BM (13–16) and also promotes PMN release into the circulation (17–19). During 2% DSS–induced colitis, high levels of IL-17A produced at the postacute stage largely promote granulopoiesis.…”

Interleukin-17 modulates myoblast cell migration by inhibiting urokinase type plasminogen activator expression through p38 mitogen-activated protein kinase

“…Activated signaling pathways induce the expression of proinflammatory cytokines, chemokines, antimicrobial peptides, growth factors and tissue remodeling enzymes (Xu and Cao, 2010). First implications about IL-17's involvement in cell differentiation were based on the findings, which demonstrated its role in hematopoiesis, suggesting that this cytokine is a stromal growth factor, which induces granulopoiesis and erythropoiesis (Schwarzenberger et al, 2000;Huang et al, 2006;Jovcić et al, 2007). Further on, considering the fact that IL-17R is ubiquitously expressed, novel non-immune functions concerning mesenchymal stem cell differentiation have been described showing that IL-17 is able to induce osteogenic (Huang et al, 2009) or to inhibit adipogenic differentiation (Shin et al, 2009) of human mesenchymal stem cells.…”