Interleukin-4 and interleukin-13: bidirectional effects on human osteoclast formation.
Osteoclasts are cells that resorb bone; they derive from macrophage colony-stimulating factor (M-CSF)-dependent hematopoietic precursors in the presence of soluble activator of NFkappaB ligand (sRANKL). Because transforming growth factor (TGF)-beta, a macrophage deactivator, enhances osteoclast formation we hypothesized that interleukin (IL)-4 and IL-13, also macrophage deactivators, should exert a similar effect. However, IL-4 and IL-13 have been reported as suppressors of murine osteoclast formation. In contrast to the effect of these molecules on murine osteoclast formation, IL-4 and IL-13 were found to be powerful inducers of osteoclast formation and bone resorption when added to human peripheral blood mononuclear cell (PBMC) cultures for 4 days. This stimulatory effect was only observed in cultures containing nonadherent PBMCs. In contrast, both molecules significantly suppressed osteoclast formation in lymphocyte-depleted cultures. These data demonstrate that the cytokine milieu and/or state of cell activation determines how cells of the osteoclast precursor respond to IL-4 and IL-13.
Scopes
J
J
Imperial College School of Medicine, London, UK.
Massey
H M
HM
Ebrahim
H
H
Horton
M A
MA
Flanagan
A M
AM
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002352:Carrier Proteins / Q000494:pharmacology; D002450:Cell Communication / Q000276:immunology; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology; D008562:Membrane Glycoproteins / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects*; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018417:Th1 Cells / Q000166:cytology; D018418:Th2 Cells / Q000166:cytology
D000970:Antineoplastic Agents; D002352:Carrier Proteins; D018793:Interleukin-13; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; D015847:Interleukin-4