Anticancer agent ABT-737 possesses anti-atopic dermatitis activity via blockade of caspase-1 in atopic dermatitis in vitro and in vivo models.
Immunopharmacol Immunotoxicol
; 40(4): 319-326, 2018 Aug.
Article
in En
| MEDLINE
| ID: mdl-29957081
ABSTRACT
OBJECTIVE:
Previous studies reported that depletion of Bcl-2 has a protective effect against allergic diseases. Furthermore, recently our study showed that anticancer drug has antiallergic inflammatory effect. An anticancer agent ABT-737 is an inhibitor of Bcl-2 and has an anti-inflammatory effect. However, the antiallergic inflammatory activity of ABT-737 is still unknown. Here, we aimed to explore the anti-atopic dermatitis (AD) activity and the mechanism of ABT-737 in AD models. MATERIALS ANDMETHODS:
HaCaT cells were used for in vitro experiments. To evaluate the effect of ABT-737 in vivo model, BalB/c mice were orally administered ABT-737 for 6 weeks in 2,4-dinitrofluorobenzene (DNFB)-induced AD-like murine model. Major assays were enzyme-linked immunosorbent assay, reverse transcription-PCR, caspase-1 assay, histamine assay, and H&E staining.RESULTS:
ABT-737 significantly decreased thymic stromal lymphopoietin (TSLP) secretion and caspase-1 activity in activated HaCaT cells. In DNFB-induced AD mice, oral administration of ABT-737 alleviated clinical severity and scratching behavior. ABT-737 decreased levels of AD-related biomarkers including IgE, histamine, TSLP, and inflammatory cytokines. In addition, ABT significantly reduced caspase-1 activity in skin lesions of AD mice. DISCUSSION ANDCONCLUSIONS:
ABT-737 elicited an anti-AD activity via suppression of caspase-1 activation in AD in vitro and in vivo models. Therefore, this study provides important information regarding the use of anticancer drugs for controlling allergic inflammatory diseases.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sulfonamides
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Biphenyl Compounds
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Keratinocytes
/
Caspase 1
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Dermatitis, Atopic
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Caspase Inhibitors
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Nitrophenols
Limits:
Animals
Language:
En
Journal:
Immunopharmacol Immunotoxicol
Journal subject:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
/
TOXICOLOGIA
Year:
2018
Type:
Article