Gene interactions and pathways from curated databases and text-mining
J Invest Dermatol 2013, PMID: 23314787

1α,25-Dihydroxyvitamin-D3-3-bromoacetate regulates AKT/mTOR signaling cascades: a therapeutic agent for psoriasis.

Datta Mitra, Ananya; Raychaudhuri, Siba P; Abria, Christine J; Mitra, Anupam; Wright, Rebecca; Ray, Rahul; Kundu-Raychaudhuri, Smriti

The efficacy of 1α,25-dihydroxyvitamin D3 (Vit-D) limits its topical use despite its profound effects on cellular differentiation, proliferation, and immunomodulation. Therefore, in search for a more effective analog of Vit-D, in this study we have evaluated the antiproliferative and proapoptotic effects of 1α,25-dihydroxyvitamin D3-3-bromoacetate (BE). Proliferation and apoptosis studies in normal human epidermal keratinocytes (NHEKs) were conducted by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), CFSE (carboxy fluorescein succinimidyl ester) dilution, and Annexin V assays. Western blot analysis and real-time PCR were performed to determine its effect on signal transduction. A reconstructed human epidermis (RHE) model was used to further validate the therapeutic role of BE in psoriasis. BE was significantly more potent than an equivalent concentration of Vit-D in inhibiting growth and survival of human keratinocytes. The antimitotic effect was found to be due to the inhibition of phosphorylation of serine/threonine protein kinase (AKT) and its downstream target, mammalian target of rapamycin (mTOR). In the RHE model, BE reversed IL-22-induced psoriasiform changes more effectively than Vit-D. Interestingly, BE inhibited the IL-22-induced gene expression of AKT1, MTOR, chemokines [IL-8 and RANTES (regulated upon activation, normal T-cell expressed and secreted)], and psoriasin (S100A7) more significantly than Vit-D. These results suggest the potential of BE as a prospective therapeutic agent for psoriasis.

Diseases/Pathways annotated by Medline MESH: Psoriasis
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Text Mining Data

psoriasin → IL-22: " Interestingly, BE inhibited the IL-22 induced gene expression of AKT1, MTOR, chemokines [ IL-8 and RANTES ( regulated upon activation, normal T-cell expressed and secreted ) ], and psoriasin ( S100A7 ) more significantly than Vit-D "

AKT1 → IL-22: " Interestingly, BE inhibited the IL-22 induced gene expression of AKT1 , MTOR, chemokines [ IL-8 and RANTES ( regulated upon activation, normal T-cell expressed and secreted ) ], and psoriasin ( S100A7 ) more significantly than Vit-D "

MTOR → IL-22: " Interestingly, BE inhibited the IL-22 induced gene expression of AKT1, MTOR , chemokines [ IL-8 and RANTES ( regulated upon activation, normal T-cell expressed and secreted ) ], and psoriasin ( S100A7 ) more significantly than Vit-D "

Manually curated Databases

No curated data.