Interleukine-17-induced inhibitory effect on late stage murine erythroid bone marrow progenitors.
Recent studies have shown that the T cell-derived cytokine, interleukin-17 (IL-17), stimulates hematopoiesis, specifically granulopoiesis inducing expansion of committed and immature progenitors in bone marrow. Our previous results pointed to its role in erythropoiesis too, demonstrating significant stimulation of BFU-E and suppression of CFU-E growth in the bone marrow from normal mice. As different sensitivities of erythroid and myeloid progenitor cells to nitric oxide (NO) were found, we considered the possibility that the observed effects of IL-17 were mediated by NO. The effects of recombinant mouse IL-17, NO donor (sodium nitroprusside - SNP) and two NO synthases inhibitors (L-NAME and aminoguanidine) on erythroid progenitor cells growth, as well as the ability of IL-17 to induce nitric oxide production in murine bone marrow cells, were examined. In addition, we tested whether the inhibition of CFU-E colony formation by IL-17 could be corrected by erythropoietin (Epo), the principal regulator of erythropoiesis. We demonstrated that IL-17 can stimulate low level production of NO in murine bone marrow cells. Exogenously added NO inhibited CFU-E colony formation, whereas both L-NAME and aminoguanidine reversed the CFU-E suppression by IL-17 in a dose-dependent manner. The inhibition of CFU-E by IL-17 was also corrected by exposure to higher levels of Epo. The data obtained demonstrated that at least some of the IL-17 effects in bone marrow related to the inhibition of CFU-E, were mediated by NO generation. The fact that Epo also overcomes the inhibitory effect of IL-17 on CFU-E suggests the need for further research on their mutual relationship and co-signalling.
Bugarski
Diana
D
Institute for Medical Research, Beograd, Serbia and Montenegro. dianab@imi.bg.ac.yu
Krstić
Aleksandra
A
Vlaski
Marija
M
Petakov
Marijana
M
Jovcić
Gordana
G
Stojanović
Nevenka
N
Milenković
Pavel
P
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004921:Erythropoietin / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D020381:Interleukin-17 / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D020641:Polymorphism, Single Nucleotide; D011994:Recombinant Proteins / Q000494:pharmacology
D004791:Enzyme Inhibitors; D020381:Interleukin-17; D020030:Nitric Oxide Donors; D011994:Recombinant Proteins; D004921:Erythropoietin; D019001:Nitric Oxide Synthase