p38 MAPK signaling mediates IL-17-induced nitric oxide synthase expression in bone marrow cells

Growth Factors. 2009 Apr;27(2):79-90. doi: 10.1080/08977190902757153.

Abstract

The effects of interleukin (IL)-17 on nitric oxide (NO) synthase (NOS) expression, as well as the participation of mitogen-activated protein kinases (MAPKs) in IL-17-mediated effects were examined in murine bone marrow cells. The results demonstrated the ability of IL-17 to upregulate the expression of mRNA for both inducible NOS and constitutive, endothelial NOS isoforms, as well as to enhance the phosphorylation of p38 MAPK. Moreover, both the NOS-inducing effect of IL-17 and the in vitro IL-17-mediated inhibition colony forming unit-erythroid (CFU-E) growth were dependent on p38 MAPK activity. The data demonstrating that the in vivo reducing effect of IL-17 on bone marrow CFU-E was prevented by co-treatment with the NOS inhibitor Nw-nitro-l-arginine methyl ester hydrochloride (L-NAME), implied that this effect is mediated through NOS activation. Besides revealing a link between the IL-17, NO, and haematopoiesis, data presented gave an insight into the mechanisms by which IL-17 exerts its modulatory effects on bone marrow cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / drug effects*
  • Bone Marrow Cells / enzymology*
  • Cells, Cultured
  • Colony-Forming Units Assay
  • Enzyme Inhibitors / pharmacology
  • Interleukin-17 / pharmacology*
  • MAP Kinase Signaling System / drug effects
  • Male
  • Mice
  • Mice, Inbred CBA
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / genetics
  • Nitric Oxide Synthase / metabolism*
  • Nitric Oxide Synthase Type II / antagonists & inhibitors
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Nitric Oxide Synthase Type III / antagonists & inhibitors
  • Nitric Oxide Synthase Type III / genetics
  • Nitric Oxide Synthase Type III / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Recombinant Proteins / pharmacology
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Enzyme Inhibitors
  • Interleukin-17
  • RNA, Messenger
  • Recombinant Proteins
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • Nos2 protein, mouse
  • Nos3 protein, mouse
  • p38 Mitogen-Activated Protein Kinases
  • NG-Nitroarginine Methyl Ester