Acanthoic acid inhibits IL-8 production via MAPKs and NF-kappaB in a TNF-alpha-stimulated human intestinal epithelial cell line.
BACKGROUND
Intestinal epithelial cells (IECs) can produce cytokines and chemokines that play an important role in the mucosal immune response. Regulation of this production is important to prevent inflammatory tissue damage. The root and stem barks of Acanthopanax species have been used as a tonic and sedative as well as in the treatment of rheumatism and diabetes. The aim of this study was to examine the inhibitory effect of acanthoic acid isolated from Acanthopanax koreanum (Araliaceae), on IL-8 production via mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-kappaB) in TNF-alpha-stimulated human colon epithelial cells.


METHODS
HT29 cells were stimulated with TNF-alpha in the presence or absence of acanthoic acid. IL-8 production was measured by enzyme-linked immunosorbent assay (ELISA) and reverse transcription-PCR (RT-PCR). MAPK activation and IkappaB/NF-kappaB expression were assessed by Western blot analysis. NF-kappaB activation was determined using immunofluorescence localization and electrophoretic mobility shift assay (EMSA).


RESULTS
Acanthoic acid suppressed TNF-alpha-induced IL-8 production in a dose-dependent manner. Furthermore, acanthoic acid inhibited TNF-alpha-induced MAPKs (p38, JNK1/2, and ERK1/2) activation, IkappaB degradation, NF-kappaB nuclear translocation, and NF-kappaB/DNA binding activity.


CONCLUSIONS
Acanthoic acid might inhibit TNF-alpha-mediated IL-8 production by blocking in both the MAPKs and NF-kappaB pathways in HT29 cells.
Kim
Jin-A
JA
Department of Oriental Pharmacy, College of Pharmacy, Wonkwang University, Iksan, Jeonbuk, 570-749, South Korea.
Kim
Dae-Ki
DK
Jin Tae
Kang
Ok-Hwa
OH
Choi
Yeon-A
YA
Choi
Suck-Chei
SC
Kim
Tae-Hyun
TH
Nah
Yong-Ho
YH
Choi
Suck-Jun
SJ
Kim
Young-Ho
YH
Bae
Ki-Hwan
KH
Lee
Young-Mi
YM
D002460:Cell Line; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D028001:Eleutherococcus / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D051550:I-kappa B Kinase; D016209:Interleukin-8 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000494:pharmacology; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D021381:Protein Transport; D012333:RNA, Messenger / Q000096:biosynthesis; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D004224:Diterpenes; D016209:Interleukin-8; D016328:NF-kappa B; D010936:Plant Extracts; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; C099958:acanthoic acid; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human; D020928:Mitogen-Activated Protein Kinases