Suppression of thymus- and activation-regulated chemokine (TARC/CCL17) production by 1,2,3,4,6-penta-O-galloyl-beta-D-glucose via blockade of NF-kappaB and STAT1 activation in the HaCaT cells.
Keratinocytes, one of major cell types in the skin, can be induced by TNF-alpha and IFN-gamma to express thymus- and activation-regulated chemokine (TARC/CCL17), which is considered to be a pivotal mediator in the inflammatory responses during the development of inflammatory skin diseases, such as atopic dermatitis (AD). In this study, we examined the effect of 1,2,3,4,6-penta-O-galloyl-beta-d-glucose (PGG), isolated from the barks of Juglans mandshurica, on TNF-alpha/IFN-gamma induced CCL17 expression in the human keratinocyte cell line HaCaT. Pretreatment of HaCaT cells with PGG suppressed TNF-alpha/IFN-gamma-induced protein and mRNA expression of CCL17. PGG significantly inhibited TNF-alpha/IFN-gamma-induced NF-kappaB activation as well as STAT1 activation. Furthermore, pretreatment with PGG resulted in significant reduction in expression of CXCL9, 10, and 11 in the HaCaT cells treated with IFN-gamma. These results suggest that PGG may exert anti-inflammatory responses by suppressing TNF-alpha and/or IFN-gamma-induced activation of NF-kappaB and STAT1 in the keratinocytes and might be a useful tool in therapy of skin inflammatory diseases.
Ju
Sung Mi
SM
Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University, Chunchon, Republic of Korea.
Song
Ha Yong
HY
Lee
Su Jin
SJ
Seo
Won Yong
WY
Sin
Dong Hyeon
DH
Goh
Ah Ra
AR
Kang
Young-Hee
YH
Kang
Il-Joon
IJ
Won
Moo-Ho
MH
Yi
Jae-Seon
JS
Kwon
Dong-Joo
DJ
Bae
Young-Soo
YS
Choi
Soo Young
SY
Park
Jinseu
J
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002460:Cell Line; D054414:Chemokine CCL17 / Q000096:biosynthesis*; D006801:Humans; D047348:Hydrolyzable Tannins / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology; D031324:Juglans / Q000737:chemistry; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; C106230:CCL17 protein, human; D054414:Chemokine CCL17; D047348:Hydrolyzable Tannins; D016328:NF-kappa B; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D014409:Tumor Necrosis Factor-alpha; C435084:pentagalloylglucose; D007371:Interferon-gamma