Hematopoiesis - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 49

T H1 -derived (IL2, Ifn γ , and gmCSF) and monocyte-derived cytokines (IL1 α and

IL1 , gmCSF, and gCSF), but induces IL1RA production by

macrophages. It stimulates B lymphocytes and mastocytes.
Interleukin-11 stimulates the proliferation of primitive stem cells as well as
commitment and differentiation of multi-lineage progenitors. It acts synergistically
to stimulate megakaryocytopoiesis and thrombopoiesis with IL3, Tpo, or SCF;
erythropoiesis with IL3, SCF, or Epo; and myeloid colony formation with SCF.
Interleukin-12 favors T H1 cell differentiation and functioning and inhibits T H2
cell differentiation. It synergizes with other hematopoietic factors to promote
proliferation of early multipotent hematopoietic progenitors and lineage-committed
precursors.
Interleukin-15 triggers the proliferation of activated B lymphocytes and their
immunoglobulin production, as well as the proliferation of NK cells and activated
CD4

β , IL6, IL8, TNF α

+ ,CD8 + T cells. Interleukin-16 is a chemokine for CD4 + cells, monocytes,

and eosinophils.
Interleukin-17 exhibits indirect hematopoietic activity by enhancing the capacity
of fibroblasts to sustain the proliferation of CD34 hematopoietic progenitors

and their differentiation into neutrophils. Main IL17 sources are CD4

+

+ T cells,

unconventional T cells in the gut, skin, and lungs,

respectively. Interleukin-18 promotes the production of Ifn

γδ T cells, and NK and γδ

and TNF.
Cytokines IL34 and gCSF (CSF3) stimulate phosphorylation of extracellular
signal-regulated kinases ERK1 and ERK2 (Vol. 4 - Chap. 6. Mitogen-Activated
Protein Kinase Modules) in human monocytes. Interleukin-34 promotes the forma-
tion of progenitor colony-forming unit macrophage (CFUm) in human bone marrow
cultures.
Proliferation and maturation of committed progenitors is controlled by late-
acting factors such as Epo, mCSF, gCSF, and IL5, most of them being lineage-
specific [ 39 ]. Progenitors at earlier stages of development are controlled by a
group of intermediate-acting lineage-non-specific cytokines: IL3, gmCSF, and IL4.
Primitive progenitors are committed by early-acting cytokines, which include IL6,
IL11, IL12, and gCSF factor. Certain cytokines are either stimulatory or inhitory.
However, others exhibit both effects such as IL4. Among inhibitors, lineage-non-
specific interferons act at various development stages, whereas TGF

γ

affects early
phases of hematopoiesis [ 92 ]. In addition, the synthesis of cytokines by the vascular
endothelium is stress dependent (Sect. 9.10 ). Steady laminar shear stress increases
the production of gmCSF by endothelial cells [ 93 ].

β

2.4.3 MicroRNAs

MicroRNA-24 is upregulated during terminal differentiation of hematopoietic cell
lines (i.e., after final cell division cycle exit). 49 It inhibits histone variant H2AX

49 When cells no longer replicate their DNA, endogenous double-stranded breaks that occur during
DNA replication and compromise genomic integrity are strongly reduced or absent.