RT Journal Article
SR Electronic
T1 Serum Amyloid A Induces Contrary Immune Responses via Formyl Peptide Receptor-Like 1 in Human Monocytes
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 241
OP 248
DO 10.1124/mol.105.022103
VO 70
IS 1
A1 Ha Young Lee
A1 Mi-Kyoung Kim
A1 Kyoung Sun Park
A1 Eun Ha Shin
A1 Seong Ho Jo
A1 Sang Doo Kim
A1 Eun Jin Jo
A1 Youl-Nam Lee
A1 Chuhee Lee
A1 Suk-Hwan Baek
A1 Yoe-Sik Bae
YR 2006
UL http://molpharm.aspetjournals.org/content/70/1/241.abstract
AB 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)-α and interleukin (IL)-10, which are proinflammatory and anti-inflammatory cytokines, respectively, in human monocytes. Low concentrations of serum amyloid A stimulated TNF-α 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-α 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-α or IL-10, and demonstrate that extracellular signal-regulated kinase and p38 kinase play counteracting roles in this process.