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

Research output: Contribution to journalArticle

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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 - Sep 18 1998

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Cyclooxygenase 2
Interleukin-4
Interleukin-10
Lipopolysaccharides
Monocytes
Phosphotransferases
p38 Mitogen-Activated Protein Kinases
Chemical activation
Phosphorylation
Mitogen-Activated Protein Kinases
Cytokines
Messenger RNA
Molecules
Macrophages
Extracellular Signal-Regulated MAP Kinases
Dinoprostone
Protein Kinases
Proteins

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

MAP kinase pathways as a route for regulatory mechanisms of IL-10 and IL-4 which inhibit COX-2 expression in human monocytes. / Niiro, Hiroaki; Otsuka, Takeshi; Ogami, Eiichi; Yamaoka, Kunihiro; Nagano, Shuji; Akahoshi, Mitsuteru; Nakashima, Hitoshi; Arinobu, Yojiro; Izuhara, Kenji; Niho, Yoshiyuki.

In: Biochemical and Biophysical Research Communications, Vol. 250, No. 2, 18.09.1998, p. 200-205.

Research output: Contribution to journalArticle

Niiro, Hiroaki ; Otsuka, Takeshi ; Ogami, Eiichi ; Yamaoka, Kunihiro ; Nagano, Shuji ; Akahoshi, Mitsuteru ; Nakashima, Hitoshi ; Arinobu, Yojiro ; Izuhara, Kenji ; Niho, Yoshiyuki. / MAP kinase pathways as a route for regulatory mechanisms of IL-10 and IL-4 which inhibit COX-2 expression in human monocytes. In: Biochemical and Biophysical Research Communications. 1998 ; Vol. 250, No. 2. pp. 200-205.
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