Induction of IL-10 synthesis by human keratinocytes through CD23 ligation: a cyclic adenosine 3',5'-monophosphate-dependent mechanism.
Ligation of the low affinity receptor for IgE, CD23/Fc epsilonRII, in human keratinocytes (HK) and monocytes induces the synthesis of proinflammatory cytokines (IL-6 and TNF-alpha), partly under the dependence of cAMP and nitric oxide pathways. Moreover, CD23 ligation induces IL-10 production in human monocytes. Since synthesis of IL-10 by HK is still a matter of debate, we investigate whether keratinocytes could produce IL-10 upon CD23 stimulation. Here, our data show that CD23 ligation induces significant IL-10 synthesis in HK, a phenomenon inhibited by cAMP antagonists, but not by inhibitors of the nitric oxide pathway. Accordingly, cAMP agonist induced significant IL-10 synthesis by HK, while nitric oxide-releasing chemical did not. Treatment of HK with anti-IL-10 mAb potentiated their CD23-mediated TNF-alpha synthesis. These data indicate that engagement of surface CD23 on human keratinocytes induces the synthesis of IL-10, which, in turn, down-regulates their proinflammatory response.
Bécherel
P A
PA
Department of Immunology, Pitié-Salpêtrière Hospital, Paris, France.
LeGoff
L
L
Francès
C
C
Chosidow
O
O
Guillosson
J J
JJ
Debré
P
P
Mossalayi
M D
MD
Arock
M
M
D000276:Adjuvants, Immunologic / Q000502:physiology; D000911:Antibodies, Monoclonal; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology*; D006801:Humans; D007231:Infant, Newborn; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D015603:Keratinocytes / Q000276:immunology* / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D017455:Receptors, IgE / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D012333:RNA, Messenger; D017455:Receptors, IgE; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009569:Nitric Oxide; D000242:Cyclic AMP