Regulatory effect of cinnamaldehyde on monocyte/macrophage-mediated inflammatory responses.
Cinnamaldehyde (CA) has been known to exhibit anti-inflammatory and anticancer effects. Although numerous pharmacological effects have been demonstrated, regulatory effect of CA on the functional activation of monocytes and macrophages has not been fully elucidated yet. To evaluate its monocyte/macrophage-mediated immune responses, macrophages activated by lipopolysaccharide (LPS), and monocytes treated with proaggregative antibodies, and extracellular matrix protein fibronectin were employed. CA was able to suppress both the production of nitric oxide (NO) and upregulation of surface levels of costimulatory molecules (CD80 and CD69) and pattern recognition receptors (toll-like receptor 2 (TLR2) and complement receptor (CR3)). In addition, CA also blocked cell-cell adhesion induced by the activation of CD29 and CD43 but not cell-fibronectin adhesion. Immunoblotting analysis suggested that CA inhibition was due to the inhibition of phosphoinositide-3-kinase (PI3K) and phosphoinositide-dependent kinase (PDK)1 as well as nuclear factor-(NF-) kappaB activation. In particular, thiol compounds with sulphydryl group, L-cysteine and dithiothreitol (DTT), strongly abrogated CA-mediated NO production and NF-kappaB activation. Therefore, our results suggest that CA can act as a strong regulator of monocyte/macrophage-mediated immune responses by thiolation of target cysteine residues in PI3K or PDK1.
Kim
Byung Hun
BH
School of Bioscience and Biotechnology, Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon 200-701, South Korea.
Lee
Yong Gyu
YG
Lee
Jaehwi
J
Lee
Joo Young
JY
Cho
Jae Youl
JY
D000171:Acrolein / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D016587:Antimutagenic Agents / Q000737:chemistry / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D051379:Mice; D015394:Molecular Structure; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D009569:Nitric Oxide / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology
D016587:Antimutagenic Agents; D016207:Cytokines; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D000171:Acrolein; C012843:cinnamaldehyde
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