Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Biochemical and biophysical research communications, 1998-09, Vol.250 (2), p.200-205

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

1998

Quelle

Elsevier Journal Backfiles on ScienceDirect (DFG Nationallizenzen)

Beschreibungen/Notizen

• 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.