RGD Reference Report - NF-kappaB and STAT3 inhibition as a therapeutic strategy in psoriasis: in vitro and in vivo effects of BTH. - Rat Genome Database

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NF-kappaB and STAT3 inhibition as a therapeutic strategy in psoriasis: in vitro and in vivo effects of BTH.

Authors: Andres, RM  Montesinos, MC  Navalon, P  Paya, M  Terencio, MC 
Citation: Andres RM, etal., J Invest Dermatol. 2013 Oct;133(10):2362-71. doi: 10.1038/jid.2013.182. Epub 2013 Apr 17.
RGD ID: 8694295
Pubmed: PMID:23594598   (View Abstract at PubMed)
DOI: DOI:10.1038/jid.2013.182   (Journal Full-text)

Benzo[b]thiophen-2-yl-3-bromo-5-hydroxy-5H-furan-2-one (BTH) is a simple and interesting synthetic derivative of petrosaspongiolide M, a natural compound isolated from a sea sponge with demonstrated potent anti-inflammatory activity through inhibition of the NF-kappaB signaling pathway. In the present study, we report the in vitro and in vivo pharmacological effect of BTH on some parameters related to the innate and adaptive response in the pathogenesis of psoriasis. BTH inhibited the release of some of the key psoriatic cytokines such as tumor necrosis factor alpha, IL-8, IL-6, and CCL27 through the downregulation of NF-kappaB in normal human keratinocytes. Moreover, it impaired signal transducers and activators of transcription 3 (STAT3) phosphorylation and translocation to the nucleus, which resulted in decreased keratinocyte proliferation. These results were confirmed in vivo in two murine models of psoriasis: the epidermal hyperplasia induced by 12-O-tetradecanoylphorbol-13-acetate and the imiquimod-induced skin inflammation model. In both cases, topical administration of BTH prevented skin infiltration and hyperplasia through suppression of NF-kappaB and STAT3 phosphorylation. Our results confirm the pivotal role of both transcriptional factors in skin inflammation, as occurs in psoriasis, and highlight the potential of small molecules as therapeutic agents for the treatment of this skin disease, with BTH being a potential candidate for future drug research.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
psoriasis treatmentISOStat3 (Mus musculus)8694295; 8694295 RGD 
psoriasis treatmentIEP 8694295 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Stat3  (signal transducer and activator of transcription 3)

Genes (Mus musculus)
Stat3  (signal transducer and activator of transcription 3)

Genes (Homo sapiens)
STAT3  (signal transducer and activator of transcription 3)


Additional Information