MAP kinase pathways as a route for regulatory mechanisms of IL-10 and IL-4 which inhibit COX-2 expression in human monocytes

Hiroaki Niiro, Takeshi Otsuka, Eiichi Ogami, Kunihiro Yamaoka, Shuji Nagano, Mitsuteru Akahoshi, Hitoshi Nakashima, Yojiro Arinobu, Kenji Izuhara, Yoshiyuki Niho

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100 Citations (Scopus)

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)E2 by 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.

Original languageEnglish
Pages (from-to)200-205
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume250
Issue number2
DOIs
Publication statusPublished - 1998 Sep 18

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Niiro, H., Otsuka, T., Ogami, E., Yamaoka, K., Nagano, S., Akahoshi, M., Nakashima, H., Arinobu, Y., Izuhara, K., & Niho, Y. (1998). MAP kinase pathways as a route for regulatory mechanisms of IL-10 and IL-4 which inhibit COX-2 expression in human monocytes. Biochemical and Biophysical Research Communications, 250(2), 200-205. https://doi.org/10.1006/bbrc.1998.9287