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Suppression of Interleukin‐12 Production through Endogenously Secreted Interleukin‐10 in Activated Dendritic Cells: Involvement of Activation of Extracellular Signal‐Regulated Protein Kinase
Author(s) -
Xia C.Q.,
Kao K. J.
Publication year - 2003
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1046/j.1365-3083.2003.01268.x
Subject(s) - mapk/erk pathway , autocrine signalling , kinase , microbiology and biotechnology , extracellular , protein kinase a , signal transduction , immune system , p38 mitogen activated protein kinases , interleukin , biology , chemistry , cytokine , immunology , receptor , biochemistry
Our recent study suggested the reverse relationship between the production of interleukin‐10 (IL‐10) and IL‐12 in dendritic cells (DCs) activated by lipopolysaccharide (LPS) or LPS plus interferon (IFN)‐γ. In the present study, a series of experiments were performed to investigate the mechanisms responsible for this reverse relationship. Our results showed that neutralization of the secreted IL‐10 by antibody could enhance the production of IL‐12. Neutralization of IL‐12 by antibody did not affect the IL‐10 production. Addition of exogenous IL‐10 suppressed the production of IL‐12 by activated DCs, and addition of exogenous IL‐12 did not affect IL‐10 production. TaqMan real‐time reverse transcriptase‐polymerase chain reaction supported the fact that the observed effects occurred at mRNA transcription level. We also found that LPS or LPS plus IFN‐γ significantly enhanced the phosphorylation of extracellular signal‐regulated protein kinase (ERK) and p38 mitogen‐activated protein kinase. In addition, inhibition of ERK by PD98059 significantly suppressed IL‐10 and increased the IL‐12 production. Exogenous IL‐10 reversed the upregulated production of IL‐12 induced by PD98059. The above findings suggest a unidirectional negative autocrine regulation of IL‐12 by IL‐10 in activated DCs and that activation of ERK involves the differential production of IL‐10 and IL‐12 by activated DCs. Thus, the regulation of differential production of IL‐10 and IL‐12 may play an important role for DCs in priming T helper 1 (Th1) or Th2 in the immune responses.