Interleukin-8 and other agonists of Gi2 proteins: autocrine paracrine growth factors for human hematopoietic progenitors acting in synergy with colony stimulating factors.
We have reviewed the current knowledge on CXC chemokine interleukin-8 (IL-8) and human hematopoiesis, and more generally on agonists of heterotrimeric Gi2 proteins as regulators of human hematopoiesis. It appears that low doses of IL-8, a Gi2-agonist produced in an autocrine fashion by normal hematopoietic progenitors, mature blood cells and leukemic cells, promotes cell survival or/and proliferation in response to hematopoietic cytokines. More importantly, inactivation of the IL-8/Gi2 pathways inhibits CD34+ cell proliferation and colony formation. Similar positive effects on hematopoiesis of other, physiological or pathological, agonists of Gi2 proteins are discussed, as well as the molecular pathways involved and the consequences of activation of other G proteins (Gq, G16) by IL-8 and other Gi2-agonists.
Hermouet
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Laboratoire d'Hematologie and INSERM U463, Groupe Récepteurs et Cytokines, Institut de Biologie, Nantes, France. Sylvie.Hermouet@nantes.inserm.fr
Corre
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Lippert
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D019898:Autocrine Communication; D004357:Drug Synergism; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology / Q000502:physiology*; D006410:Hematopoiesis / Q000187:drug effects / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000502:physiology*; D020962:Heterotrimeric GTP-Binding Proteins / Q000819:agonists / Q000502:physiology*; D006801:Humans; D016209:Interleukin-8 / Q000494:pharmacology / Q000502:physiology*; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology / Q000502:physiology*; D019899:Paracrine Communication; D011518:Proto-Oncogene Proteins / Q000819:agonists / Q000502:physiology*
D016209:Interleukin-8; D011518:Proto-Oncogene Proteins; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C498015:GNAI2 protein, human; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D020962:Heterotrimeric GTP-Binding Proteins