Abstract
Eotaxin/CCL-11 is a major chemoattractant that contributes to eosinophilic inflammation in asthma. Glucocorticoids inhibit inflammation, but long-time exposure may cause paradoxical adverse effects by augmenting eotaxin/CCL-11production. The aim of this study was to determine if 7,4′-dihydroxyflavone (7,4′-DHF), the eotaxin/CCL11 inhibitor isolated from Glycyrrhiza uralensis, reduces in vitro eotaxin production induced by long-time dexamethasone (Dex) exposure, and if so, to elucidate the mechanisms of this inhibition. Human lung fibroblast-1 cells were used to identify the potency of 7,4′-DHF compared with other compounds from G. uralensis, to compare 7,4′-DHF with Dex on eotaxin production following 24-h short-time culture and 72-h longer-time (LT) culture, and to determine the effects of the 7,4′-DHF on Dex LT culture augmented eotaxin production and molecule mechanisms. 7,4′-DHF was the most potent eotaxin/CCL-11 inhibitor among the ten compounds and provided continued suppression. In contrast to short-time culture, Dex LT culture increased constitutively, and IL-4/TNF-α stimulated eotaxin/CCL11 production by human lung fibroblast-1 cells. This adverse effect was abrogated by 7,4′-DHF co-culture. 7,4′-DHF significantly inhibited Dex LT culture augmentation of p-STAT6 and impaired HDAC2 expression. This study demonstrated that 7,4′-DHF has the ability to consistently suppress eotaxin production and prevent Dex-paradoxical adverse effects on eotaxin production.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 449-458 |
| Number of pages | 10 |
| Journal | Phytotherapy Research |
| Volume | 31 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 1 2017 |
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Keywords
- corticosteroids
- Glycyrrhiza uralensis
- lung fibroblasts
- STAT6
ASJC Scopus subject areas
- Pharmacology
Cite this
The Flavonoid 7,4′-Dihydroxyflavone Prevents Dexamethasone Paradoxical Adverse Effect on Eotaxin Production by Human Fibroblasts. / Liu, Changda; Yang, Nan; Chen, Xiaoke; Tversky, Jody R; Zhan, Jixun; Chehade, Mirna; Miller, Rachel L.; Li, Xiu Min.
In: Phytotherapy Research, Vol. 31, No. 3, 01.03.2017, p. 449-458.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The Flavonoid 7,4′-Dihydroxyflavone Prevents Dexamethasone Paradoxical Adverse Effect on Eotaxin Production by Human Fibroblasts
AU - Liu, Changda
AU - Yang, Nan
AU - Chen, Xiaoke
AU - Tversky, Jody R
AU - Zhan, Jixun
AU - Chehade, Mirna
AU - Miller, Rachel L.
AU - Li, Xiu Min
PY - 2017/3/1
Y1 - 2017/3/1
N2 - Eotaxin/CCL-11 is a major chemoattractant that contributes to eosinophilic inflammation in asthma. Glucocorticoids inhibit inflammation, but long-time exposure may cause paradoxical adverse effects by augmenting eotaxin/CCL-11production. The aim of this study was to determine if 7,4′-dihydroxyflavone (7,4′-DHF), the eotaxin/CCL11 inhibitor isolated from Glycyrrhiza uralensis, reduces in vitro eotaxin production induced by long-time dexamethasone (Dex) exposure, and if so, to elucidate the mechanisms of this inhibition. Human lung fibroblast-1 cells were used to identify the potency of 7,4′-DHF compared with other compounds from G. uralensis, to compare 7,4′-DHF with Dex on eotaxin production following 24-h short-time culture and 72-h longer-time (LT) culture, and to determine the effects of the 7,4′-DHF on Dex LT culture augmented eotaxin production and molecule mechanisms. 7,4′-DHF was the most potent eotaxin/CCL-11 inhibitor among the ten compounds and provided continued suppression. In contrast to short-time culture, Dex LT culture increased constitutively, and IL-4/TNF-α stimulated eotaxin/CCL11 production by human lung fibroblast-1 cells. This adverse effect was abrogated by 7,4′-DHF co-culture. 7,4′-DHF significantly inhibited Dex LT culture augmentation of p-STAT6 and impaired HDAC2 expression. This study demonstrated that 7,4′-DHF has the ability to consistently suppress eotaxin production and prevent Dex-paradoxical adverse effects on eotaxin production.
AB - Eotaxin/CCL-11 is a major chemoattractant that contributes to eosinophilic inflammation in asthma. Glucocorticoids inhibit inflammation, but long-time exposure may cause paradoxical adverse effects by augmenting eotaxin/CCL-11production. The aim of this study was to determine if 7,4′-dihydroxyflavone (7,4′-DHF), the eotaxin/CCL11 inhibitor isolated from Glycyrrhiza uralensis, reduces in vitro eotaxin production induced by long-time dexamethasone (Dex) exposure, and if so, to elucidate the mechanisms of this inhibition. Human lung fibroblast-1 cells were used to identify the potency of 7,4′-DHF compared with other compounds from G. uralensis, to compare 7,4′-DHF with Dex on eotaxin production following 24-h short-time culture and 72-h longer-time (LT) culture, and to determine the effects of the 7,4′-DHF on Dex LT culture augmented eotaxin production and molecule mechanisms. 7,4′-DHF was the most potent eotaxin/CCL-11 inhibitor among the ten compounds and provided continued suppression. In contrast to short-time culture, Dex LT culture increased constitutively, and IL-4/TNF-α stimulated eotaxin/CCL11 production by human lung fibroblast-1 cells. This adverse effect was abrogated by 7,4′-DHF co-culture. 7,4′-DHF significantly inhibited Dex LT culture augmentation of p-STAT6 and impaired HDAC2 expression. This study demonstrated that 7,4′-DHF has the ability to consistently suppress eotaxin production and prevent Dex-paradoxical adverse effects on eotaxin production.
KW - corticosteroids
KW - Glycyrrhiza uralensis
KW - lung fibroblasts
KW - STAT6
UR - http://www.scopus.com/inward/record.url?scp=85014308722&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85014308722&partnerID=8YFLogxK
U2 - 10.1002/ptr.5767
DO - 10.1002/ptr.5767
M3 - Article
C2 - 28102022
AN - SCOPUS:85014308722
VL - 31
SP - 449
EP - 458
JO - Phytotherapy Research
JF - Phytotherapy Research
SN - 0951-418X
IS - 3
ER -