Involvement of NF-kappaB in the inhibitory actions of Platycarya strobilacea on the TNF-alpha-induced monocyte adhesion to colon epithelial cells and chemokine expression.
Oxidative stress and the activation of nuclear factor (NF)-kappaB play crucial roles in the pathogenesis of inflammatory bowel disease (IBD). In the present study, we examined the effects of the ethanol extract of Platycarya strobilacea Sieb. stem (EPS) on TNF-alpha-induced monocyte adhesion to HT29 human colon epithelial cells, an initial step of colon inflammation. EPS contained high amount of polyphenols (0.241+/-0.017 mg of catechin equivalent/g of extract) and showed substantial DPPH radical scavenging activity. In addition, EPS significantly suppressed TNF-alpha-induced reactive oxygen species (ROS) increase. Moreover, TNF-alpha-induced monocyte adhesion to HT29 colon epithelial cells was significantly suppressed by EPS in a concentration-dependent manner. The reduced adhesion by EPS was correlated with suppressed expression of MCP-1 and IL-8, the major chemokines in IBD. EPS also prevented the TNF-alpha-induced nuclear translocation of NF-kappaB, one of the redox-sensitive transcription factors, in a concentration-dependent manner. Taken together, our results suggest that the anti-oxidant components of EPS prevent TNF-alpha-induced NF-kappaB activation, chemokine induction, and monocyte adhesion at the site of intestinal inflammation.
Babu
Dinesh
D
College of Pharmacy, Yeungnam University, Gyeongsan, 712-749, Korea.
Lee
Jong Suk
JS
Park
Su-Young
SY
Thapa
Dinesh
D
Choi
Mi Kyoung
MK
Kim
Ah Ra
AR
Park
Young-Joon
YJ
Kim
Jung-Ae
JA
D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D000975:Antioxidants / Q000302:isolation & purification / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects*; D018932:Chemokine CCL2 / Q000378:metabolism; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D003106:Colon / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology; D019073:HT29 Cells; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D029525:Juglandaceae / Q000737:chemistry; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D010636:Phenols / Q000494:pharmacology; D024301:Plant Bark; D059808:Polyphenols; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D020298:U937 Cells
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; C111835:CCL2 protein, human; C508606:CXCL8 protein, human; D018932:Chemokine CCL2; D018925:Chemokines; D005419:Flavonoids; D016209:Interleukin-8; D016328:NF-kappa B; D010636:Phenols; D059808:Polyphenols; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha