Transforming growth factor beta and interleukin-1: a paradigm for opposing regulation of haemopoiesis.
The polypeptide cytokines, IL-1 and TGF-beta affect nearly every tissue and cell type in the body. IL-1 is the prototype of the proinflammatory molecule while TGF-beta is essentially anti-inflammatory. IL-1 is part of the cascade of cytokines that are produced during microbial invasion or bodily injury and enhance a variety of host responses, particularly in the immunological and haemopoietic systems, while TGF-beta acts as an inhibitor of these responses. At several levels, IL-1 and TGF-beta act in opposition to one another. IL-1 stimulates the expression of many genes in lymphoid and marrow stromal cells that stimulate haemopoietic cell growth and differentiation, while TGF-beta inhibits these IL-1 mediated effects. Also, TGF-beta stimulates secretion of the IL-1Ra. In addition, IL-1 induces the cell surface expression of cytokine receptors on lymphoid and haemopoietic cells, while TGF-beta dramatically inhibits the cell surface expression of these receptors, including the IL-1 receptor. Finally, IL-1 augments lymphoid and haemopoietic cell growth and TGF-beta potently inhibits this proliferation. The interactions of these cytokines serve to illustrate that the net balance of stimulatory and inhibitory signals determines the fate of a given cell which may be responsible for regulating homeostatic cell growth (Figure 1). Thus, the regulation of cytokine production and/or antagonism of their effects continues to be a therapeutic goal in the treatment of many diseases.
Ruscetti
F W
FW
Dubois
C M
CM
Jacobsen
S E
SE
Keller
J R
JR
D000818:Animals; D001854:Bone Marrow Cells; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003114:Colony-Forming Units Assay; D016207:Cytokines / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D006410:Hematopoiesis / Q000502:physiology*; D016298:Hematopoietic Cell Growth Factors / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology / Q000502:physiology*; D007938:Leukemia / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects; D008223:Lymphoma / Q000473:pathology; D051379:Mice; D008954:Models, Biological; D009924:Organ Culture Techniques; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology / Q000502:physiology*
D016207:Cytokines; D016298:Hematopoietic Cell Growth Factors; D007375:Interleukin-1; D011956:Receptors, Cell Surface; D016212:Transforming Growth Factor beta