Suppression of thymus- and activation-regulated chemokine (TARC/CCL17) production by 3-O-β-D-glucopyanosylspinasterol via blocking NF-κB and STAT1 signaling pathways in TNF-α and IFN-γ-induced HaCaT keratinocytes

Mi-ra Jung, Tae Hoon Lee, Myun-Ho Bang, Hakwon Kim, Youngsook Son, Dae Kyun Chung, Jiyoung Kim
Biochemical and Biophysical Research Communications 2012 October 19, 427 (2): 236-41
A phytosterol derivative, 3-O-β-D-glucopyanosylspinasterol (spinasterol-Glc) isolated from leaves of Stewartia koreana was reported to inhibit LPS-induced cytokine production in macrophage cells. Thymus and activation regulated chemokine (TARC/CCL17) is produced in response to pro-inflammatory cytokines in keratinocytes, which is implicated in the development of inflammatory skin diseases. In present study, we investigated the effect of spinasterol-Glc on production of TARC/CCL17 induced by TNF-α and IFN-γ in human HaCaT keratinocytes. Spinasterol-Glc inhibited the mRNA and protein expression of TARC/CCL17 induced by TNF-α/IFN-γ in a dose-dependent manner. Inhibitors of c-Raf-1, p38 MAPK, and JAK2, suppressed the TNF-α/IFN-γ-induced production of TARC/CCL17, and phosphorylation of these signaling molecules were attenuated by spinasterol-Glc. The compound also inhibited phosphorylation of IKKα/β and IκB-α, and reduced translocation of NF-κB to the nucleus. We demonstrated that spinasterol-Glc suppressed the NF-κB-driven and the GAS-driven expression of luciferase reporter gene induced by TNF-α and IFN-γ. In addition, spinasterol-Glc inhibited the DNA binding of NF-κB and STAT1 to its cognate binding site. These results suggest that spinasterol-Glc has effective inhibitory effects on production of TARC/CCL17 in keratinocytes via inhibition of NF-κB as well as STAT activation, and could be utilized for development of a potential therapeutic agent against skin inflammatory diseases.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"