Abstract
Exposure to toxic halogenated polyaromatic hydrocarbons, of which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the most potent, induces diverse skin pathologies in humans, including chloracne, hyperkeratosis, hamartomas, etc. While the toxic effects of TCDD have been extensively studied, effective approaches to their treatment are still lacking. Retinoids are commonly used in therapy of acneiform skin diseases. In vitro, retinoids elicit antagonistic effects on keratinocyte differentiation and proliferation, as compared to TCDD, suggesting their potential in treatment of TCDD-induced skin lesions. Nevertheless, the modulation of TCDD activity in skin by retinoids in vivo was never reported. We have used N-TERT keratinocyte cell line and hairless (hr) mice to determine if retinoic acid (RA) can lessen or reverse TCDD-induced effects in vitro and in vivo. RA co-treatment suppressed TCDD-induced changes in the expression of differentiation-associated genes and N-TERT keratinocyte viability in vitro. However, in hairless mice (in vivo), RA/TCDD co-treatment produced more severe effects, than treatment with either of the two compounds individually. RA/TCDD co-application to mouse skin strongly stimulated keratinocyte proliferation, resulting in dramatic epidermal hyperplasia. It has also led to massive immune cell infiltration into the dermis, and increased mRNA expression of inflammation markers, including IL1β, IL6 and S100A7. Thus, retinoids not only appeared ineffective in treatment of TCDD-induced skin lesions in hairless mice, but also resulted in their exaggeration. These in vivo results question previous cell culture-based claims that RA may reduce TCDD-induced skin effects and caution against the reliance on in vitro data in TCDD toxicology research.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 854-861 |
| Number of pages | 8 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 506 |
| Issue number | 4 |
| DOIs | |
| State | Published - Dec 2 2018 |
| Externally published | Yes |
Fingerprint
Keywords
- Ahr
- Chloracne
- Dioxin
- hr
- Psoriasis
ASJC Scopus subject areas
- Biophysics
- Biochemistry
- Molecular Biology
- Cell Biology
Cite this
Retinoic acid co-treatment aggravates severity of dioxin-induced skin lesions in hairless mice via induction of inflammatory response. / Rudyak, Stanislav G.; Usakin, Lev A.; Tverye, Ekaterina A.; Orekhov, Anton S.; Belushkina, Natalya N.; Paus, Ralf; Paltsev, Mikhail A.; Panteleyev, Andrey A.
In: Biochemical and Biophysical Research Communications, Vol. 506, No. 4, 02.12.2018, p. 854-861.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Retinoic acid co-treatment aggravates severity of dioxin-induced skin lesions in hairless mice via induction of inflammatory response
AU - Rudyak, Stanislav G.
AU - Usakin, Lev A.
AU - Tverye, Ekaterina A.
AU - Orekhov, Anton S.
AU - Belushkina, Natalya N.
AU - Paus, Ralf
AU - Paltsev, Mikhail A.
AU - Panteleyev, Andrey A.
PY - 2018/12/2
Y1 - 2018/12/2
N2 - Exposure to toxic halogenated polyaromatic hydrocarbons, of which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the most potent, induces diverse skin pathologies in humans, including chloracne, hyperkeratosis, hamartomas, etc. While the toxic effects of TCDD have been extensively studied, effective approaches to their treatment are still lacking. Retinoids are commonly used in therapy of acneiform skin diseases. In vitro, retinoids elicit antagonistic effects on keratinocyte differentiation and proliferation, as compared to TCDD, suggesting their potential in treatment of TCDD-induced skin lesions. Nevertheless, the modulation of TCDD activity in skin by retinoids in vivo was never reported. We have used N-TERT keratinocyte cell line and hairless (hr) mice to determine if retinoic acid (RA) can lessen or reverse TCDD-induced effects in vitro and in vivo. RA co-treatment suppressed TCDD-induced changes in the expression of differentiation-associated genes and N-TERT keratinocyte viability in vitro. However, in hairless mice (in vivo), RA/TCDD co-treatment produced more severe effects, than treatment with either of the two compounds individually. RA/TCDD co-application to mouse skin strongly stimulated keratinocyte proliferation, resulting in dramatic epidermal hyperplasia. It has also led to massive immune cell infiltration into the dermis, and increased mRNA expression of inflammation markers, including IL1β, IL6 and S100A7. Thus, retinoids not only appeared ineffective in treatment of TCDD-induced skin lesions in hairless mice, but also resulted in their exaggeration. These in vivo results question previous cell culture-based claims that RA may reduce TCDD-induced skin effects and caution against the reliance on in vitro data in TCDD toxicology research.
AB - Exposure to toxic halogenated polyaromatic hydrocarbons, of which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the most potent, induces diverse skin pathologies in humans, including chloracne, hyperkeratosis, hamartomas, etc. While the toxic effects of TCDD have been extensively studied, effective approaches to their treatment are still lacking. Retinoids are commonly used in therapy of acneiform skin diseases. In vitro, retinoids elicit antagonistic effects on keratinocyte differentiation and proliferation, as compared to TCDD, suggesting their potential in treatment of TCDD-induced skin lesions. Nevertheless, the modulation of TCDD activity in skin by retinoids in vivo was never reported. We have used N-TERT keratinocyte cell line and hairless (hr) mice to determine if retinoic acid (RA) can lessen or reverse TCDD-induced effects in vitro and in vivo. RA co-treatment suppressed TCDD-induced changes in the expression of differentiation-associated genes and N-TERT keratinocyte viability in vitro. However, in hairless mice (in vivo), RA/TCDD co-treatment produced more severe effects, than treatment with either of the two compounds individually. RA/TCDD co-application to mouse skin strongly stimulated keratinocyte proliferation, resulting in dramatic epidermal hyperplasia. It has also led to massive immune cell infiltration into the dermis, and increased mRNA expression of inflammation markers, including IL1β, IL6 and S100A7. Thus, retinoids not only appeared ineffective in treatment of TCDD-induced skin lesions in hairless mice, but also resulted in their exaggeration. These in vivo results question previous cell culture-based claims that RA may reduce TCDD-induced skin effects and caution against the reliance on in vitro data in TCDD toxicology research.
KW - Ahr
KW - Chloracne
KW - Dioxin
KW - hr
KW - Psoriasis
UR - http://www.scopus.com/inward/record.url?scp=85055737078&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85055737078&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2018.10.126
DO - 10.1016/j.bbrc.2018.10.126
M3 - Article
VL - 506
SP - 854
EP - 861
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 4
ER -