Interleukin-10 inhibits IgE-mediated nitric oxide synthase induction and cytokine synthesis in normal human keratinocytes.
Human keratinocytes (HK) generate nitric oxide (NO) and proinflammatory mediators following activation with either IgE/anti-IgE immune complexes or a combination of lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). Recently, interleukin-10 (IL-10) has been shown to down-regulate various inflammatory responses and to be secreted by lymphocytes and dendritic cells during skin inflammatory reactions. We show here that IL-10 down-regulates the production of tumor necrosis factor (TNF)-alpha and IL-6 by activated HK. Also, induction of inducible nitric oxide synthase (iNOS) expression in HK by IgE/anti-IgE or LPS/IFN-gamma is significantly reduced by the addition of IL-10. This effect is dose dependent and correlates with reduction of iNOS mRNA production and enzyme level. Therefore, IL-10 down-regulates NO-mediated HK inflammatory responses and may thus participate in the regulation of the skin immune network.
Bécherel
P A
PA
Molecular Immuno-Hematology Group (CNRS URA625), CHU Pitié-Salpêtrière, Paris, France.
Le Goff
L
L
Ktorza
S
S
Ouaaz
F
F
Mencia-Huerta
J M
JM
Dugas
B
B
Debré
P
P
Mossalayi
M D
MD
Arock
M
M
D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D001483:Base Sequence; D002478:Cells, Cultured; D003864:Depression, Chemical; D004790:Enzyme Induction / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007073:Immunoglobulin E / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects* / Q000201:enzymology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism
D000888:Antibodies, Anti-Idiotypic; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C026408:anti-IgE antibodies; D016753:Interleukin-10; D009569:Nitric Oxide; D007073:Immunoglobulin E; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase