Serum amyloid A induces contrary immune responses via formyl peptide receptor-like 1 in human monocytes.

Abstract

Although the level of serum amyloid A has been reported to be up-regulated during inflammatory response, the role of serum amyloid A on the regulation of inflammation and immune response has not been elucidated. We found that serum amyloid A stimulated the production of tumor necrosis factor (TNF)-alpha and interleukin (IL)-10, which are proinflammatory and anti-inflammatory cytokines, respectively, in human monocytes. Low concentrations of serum amyloid A stimulated TNF-alpha production with maximal activity at 6 h after stimulation, whereas high concentrations of serum amyloid A stimulated IL-10 production with maximal activity at 12 h. The activations of the two cytokines by serum amyloid A occurred at both the transcription and translational levels. Signaling events induced by serum amyloid A included the activation of two mitogen-activated protein kinases (extracellular signal-regulated kinase and p38 kinase), which were found to be required for TNF-alpha and IL-10 production, respectively. The stimulation of formyl peptide receptor-like-1-expressing RBL-2H3 cells, but not of vector-expressing RBL-2H3 cells with serum amyloid A, induced mitogen-activated protein kinases activation and the accumulation of the RNAs of these two cytokines. Together, our findings suggest that serum amyloid A modulates contrary immune responses via formyl peptide receptor-like 1, by inducing TNF-alpha or IL-10, and demonstrate that extracellular signal-regulated kinase and p38 kinase play counteracting roles in this process.

• Authors: Ha Young Lee, Mi-Kyoung Kim, Kyoung Sun Park, Eun Ha Shin, Seong Ho Jo, Sang Doo Kim, Eun Jin Jo, Youl-Nam Lee, Chuhee Lee, Suk-Hwan Baek, Yoe-Sik Bae
• Journal: Molecular pharmacology (Mol Pharmacol) Vol. 70 Issue 1 Pg. 241-8 (Jul 2006) ISSN: 0026-895X [Print] United States
• PMID: 16569709 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 3-(4-methylphenylsulfonyl)-2-propenenitrile
• Chromones
• Enzyme Inhibitors
• Flavonoids
• Imidazoles
• Morpholines
• NF-kappa B
• Nitriles
• Phosphoinositide-3 Kinase Inhibitors
• Pyridines
• RNA, Messenger
• Receptors, Formyl Peptide
• Serum Amyloid A Protein
• Sulfones
• Tumor Necrosis Factor-alpha
• Interleukin-10
• 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
• Extracellular Signal-Regulated MAP Kinases
• p38 Mitogen-Activated Protein Kinases
• SB 203580
• 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one

Topics

• Animals
• Blotting, Western
• Cell Line, Tumor
• Chromones (pharmacology)
• Dose-Response Relationship, Drug
• Enzyme Activation (drug effects)
• Enzyme Inhibitors (pharmacology)
• Extracellular Signal-Regulated MAP Kinases (antagonists & inhibitors, metabolism)
• Flavonoids (pharmacology)
• Humans
• Imidazoles (pharmacology)
• Interleukin-10 (biosynthesis, genetics)
• Monocytes (drug effects, immunology, metabolism)
• Morpholines (pharmacology)
• NF-kappa B (antagonists & inhibitors, metabolism)
• Nitriles (pharmacology)
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphoinositide-3 Kinase Inhibitors
• Phosphorylation (drug effects)
• Pyridines (pharmacology)
• RNA, Messenger (genetics, metabolism)
• Receptors, Formyl Peptide (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Serum Amyloid A Protein (pharmacology)
• Sulfones (pharmacology)
• Tumor Necrosis Factor-alpha (biosynthesis, genetics)
• p38 Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism)