PMID- 23314787
OWN - NLM
STAT- MEDLINE
DCOM- 20130717
LR  - 20231213
IS  - 1523-1747 (Electronic)
IS  - 0022-202X (Linking)
VI  - 133
IP  - 6
DP  - 2013 Jun
TI  - 1alpha,25-Dihydroxyvitamin-D3-3-bromoacetate regulates AKT/mTOR signaling cascades: a 
      therapeutic agent for psoriasis.
PG  - 1556-64
LID - 10.1038/jid.2013.3 [doi]
AB  - The efficacy of 1alpha,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 
      1alpha,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.
FAU - Datta Mitra, Ananya
AU  - Datta Mitra A
AD  - IM/Rheumatology, Allergy and Clinical Immunology, University of California Davis 
      School of Medicine, Sacramento, California, USA.
FAU - Raychaudhuri, Siba P
AU  - Raychaudhuri SP
FAU - Abria, Christine J
AU  - Abria CJ
FAU - Mitra, Anupam
AU  - Mitra A
FAU - Wright, Rebecca
AU  - Wright R
FAU - Ray, Rahul
AU  - Ray R
FAU - Kundu-Raychaudhuri, Smriti
AU  - Kundu-Raychaudhuri S
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130111
PL  - United States
TA  - J Invest Dermatol
JT  - The Journal of investigative dermatology
JID - 0426720
RN  - 0 (1,25-dihydroxyvitamin D3-3-bromoacetate)
RN  - 0 (CXCL8 protein, human)
RN  - 0 (Chemokine CCL5)
RN  - 0 (Interleukin-8)
RN  - 0 (Interleukins)
RN  - 0 (S100 Calcium Binding Protein A7)
RN  - 0 (S100 Proteins)
RN  - 0 (S100A7 protein, human)
RN  - 0 (Vitamins)
RN  - 1406-16-2 (Vitamin D)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (AKT1 protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - FXC9231JVH (Calcitriol)
SB  - IM
MH  - Apoptosis/drug effects
MH  - Calcitriol/*analogs & derivatives/pharmacology
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Chemokine CCL5/genetics/metabolism
MH  - Epidermal Cells
MH  - Gene Expression/drug effects/physiology
MH  - Humans
MH  - Interleukin-8/genetics/metabolism
MH  - Interleukins/metabolism
MH  - Keratinocytes/cytology/*drug effects/metabolism
MH  - Phosphorylation/drug effects/physiology
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Psoriasis/*drug therapy/metabolism/pathology
MH  - S100 Calcium Binding Protein A7
MH  - S100 Proteins/genetics/metabolism
MH  - Signal Transduction/*drug effects/physiology
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Vitamin D/pharmacology
MH  - Vitamins/pharmacology
MH  - Interleukin-22
EDAT- 2013/01/15 06:00
MHDA- 2013/07/19 06:00
CRDT- 2013/01/15 06:00
PHST- 2013/01/15 06:00 [entrez]
PHST- 2013/01/15 06:00 [pubmed]
PHST- 2013/07/19 06:00 [medline]
AID - S0022-202X(15)36308-9 [pii]
AID - 10.1038/jid.2013.3 [doi]
PST - ppublish
SO  - J Invest Dermatol. 2013 Jun;133(6):1556-64. doi: 10.1038/jid.2013.3. Epub 2013 
      Jan 11.