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MAP Kinase Pathways as a Route for Regulatory Mechanisms of IL-10 and IL-4 Which Inhibit COX-2 Expression in Human Monocytes,☆☆,

https://doi.org/10.1006/bbrc.1998.9287Get rights and content

Abstract

Mitogen-activated protein kinases (MAPKs) are activated by various extracellular stimuli and play an important role in regulating the expression of proinflammatory molecules in monocytes/macrophages. We first questioned whether MAPK activation is involved in cyclooxygenase (COX)-2 expression in lipopolysaccharide (LPS)-stimulated human monocytes. LPS induced the expression of COX-2 protein and COX-2 mRNA as well as the phosphorylation and activation of extracellular signal-regulated protein kinase (ERK)2 and p38 MAPK in monocytes. The induction of COX-2 mRNA, COX-2 protein, and prostaglandin (PG)E2by LPS was inhibited by the specific inhibitors of ERK and p38 MAPK, suggesting that the activation of ERK2 and p38 MAPK is involved in COX-2 expression in LPS-stimulated monocytes. Since we previously showed that interleukin (IL)-10 and IL-4 similarly inhibited COX-2 expression in LPS-stimulated monocytes, we next questioned whether these cytokines regulate the phosphorylation and activation of ERK2 and p38 MAPK in LPS-stimulated monocytes. Interestingly, LPS-induced phosphorylation and activation of ERK2 was significantly inhibited by IL-4 and IL-10, while that of p38 MAPK was inhibited by IL-10, but not IL-4. These results suggest that the mechanisms of inhibition by IL-10 and IL-4 of the LPS-induced expression of proinflammatory molecules could be ascribed to the regulatory effects of both cytokines on MAPK activation.

References (29)

  • B. Su et al.

    Curr. Opin. Immunol.

    (1996)
  • H. Niiro et al.

    Blood

    (1995)
  • H. Niiro et al.

    Blood

    (1997)
  • P. Wang et al.

    J. Biol. Chem.

    (1995)
  • Z. Guan et al.

    J. Biol. Chem.

    (1997)
  • J.C. Lee et al.

    J. Leukoc. Biol.

    (1996)
  • J.A. Nick et al.

    J. Immunol.

    (1996)
  • J.S. Sanghera et al.

    J. Immunol.

    (1996)
  • J. Hambleton et al.

    Proc. Natl. Acad. Sci. USA

    (1996)
  • M. Pouliot et al.

    J. Immunol.

    (1997)
  • D.M. Rose et al.

    J. Immunol.

    (1997)
  • K.W. Moore et al.

    Annu. Rev. Immunol.

    (1993)
  • P.H. Hart et al.

    Proc. Natl. Acad. Sci. USA

    (1989)
  • Y. Niho et al.

    Molecular Biology of Haematopoiesis

    (1994)
  • Cited by (0)

    This work was supported in part by grants-in-aid for Scientific Research on Priority Areas from the Ministry of Education, Science, Sports and Culture of Japan and by the Special Coordination Funds for Science and Technology.

    ☆☆

    Abbreviations: MAPK, mitogen-activated protein kinase; COX, cyclooxygenase; LPS, lipopolysaccharide; ERK, extracellular signal-regulated protein kinase; PG, prostaglandin; IL, interleukin; JNK, c-Jun N-terminal kinase; TPA, 12-O-tetradecanoylphorbol-13-acetate; FMLP, N-formyl-methionyl-leucyl-phenylalanine; TNF, tumor necrosis factor; RIA, radioimmunoassay; G3PDH, glyceraldehyde-3-phosphate dehydrogenase

    N. G. AbrahamR. K. ShadduckA. S. LevineF. Takaku

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