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IRAK1/4-Targeted Anti-Inflammatory Action of Caffeic Acid
- Source :
- Mediators of Inflammation, Vol 2013 (2013), Mediators of Inflammation
- Publication Year :
- 2013
- Publisher :
- Hindawi Limited, 2013.
-
Abstract
- Caffeic acid (CA) is a phenolic compound that is frequently present in fruits, grains, and dietary supplements. Although CA has been reported to display various biological activities such as anti-inflammatory, anti-cancer, anti-viral, and anti-oxidative effects, the action mechanism of CA is not yet fully elucidated. In this study, the anti-inflammatory action mechanism of CA was examined in lipopolysaccharide (LPS) treated macrophages (RAW264.7 cells) and HCl/EtOH-induced gastritis. CA was found to diminish nitric oxide (NO) and prostaglandin E2(PGE2) production in LPS-stimulated RAW264.7 cells. Additionally, mRNA levels of tumor necrosis factor (TNF)-α, cyclooxygenase (COX)-2, and inducible NO synthase (iNOS) were downregulated by CA. CA also strongly suppressed the nuclear translocation of AP-1 family proteins and the related upstream signaling cascade composed of interleukin-1 receptor-associated kinase 1 (IRAK1), IRAK4, TGF-β-activated kinase 1 (TAK1), mitogen-activated protein kinase kinase 4/7 (MKK4/7), and c-Jun N-terminal kinase (JNK). In a direct kinase assay, CA was revealed to directly inhibit IRAK1 and IRAK4. CA also ameliorated HCl/EtOH-induced gastric symptoms via the suppression of JNK, IRAK1, and IRAK4. Therefore, our data strongly suggest that CA acts as an anti-inflammatory drug by directly suppressing IRAK1 and IRAK4.
- Subjects :
- Male
Article Subject
Immunology
Anti-Inflammatory Agents
Nitric Oxide Synthase Type II
Biology
Pharmacology
Nitric oxide
Mice
chemistry.chemical_compound
Caffeic Acids
medicine
Caffeic acid
lcsh:Pathology
Animals
Humans
Prostaglandin E2
Protein kinase A
Cells, Cultured
Mice, Inbred ICR
Tumor Necrosis Factor-alpha
Kinase
JNK Mitogen-Activated Protein Kinases
IRAK1
Cell Biology
IRAK4
Transcription Factor AP-1
HEK293 Cells
Interleukin-1 Receptor-Associated Kinases
chemistry
Biochemistry
Tumor necrosis factor alpha
Research Article
medicine.drug
lcsh:RB1-214
Subjects
Details
- Language :
- English
- ISSN :
- 14661861 and 09629351
- Volume :
- 2013
- Database :
- OpenAIRE
- Journal :
- Mediators of Inflammation
- Accession number :
- edsair.doi.dedup.....d05c1f17672061f4b857ed05784973a1