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Blocking mTOR Signalling with Rapamycin Ameliorates Imiquimod-induced Psoriasis in Mice
- Source :
- Acta Dermato-Venereologica, Vol 97, Iss 9, Pp 1087-1094 (2017)
- Publication Year :
- 2017
- Publisher :
- Society for Publication of Acta Dermato-Venereologica, 2017.
-
Abstract
- The mTOR (mechanistic target of rapamycin) inhibitor rapamycin has long been known for its immune suppressive properties, but it has shown limited therapeutic success when given systemically to patients with psoriasis. Recent data have shown that the mTOR pathway is hyperactivated in lesional psoriatic skin, which probably contributes to the disease by interfering with maturation of keratinocytes. This study investigated the effect of topical rapamycin treatment in an imiquimod-induced psoriatic mouse model. The disease was less severe if the mice had received rapamycin treatment. Immunohistological analysis revealed that rapamycin not only prevented the activation of mTOR signalling (P-mTOR and P-S6 levels), but almost normalized the expression of epidermal differentiation markers. In addition, the influx of innate immune cells into the draining lymph nodes was partially reduced by rapamycin treatment. These data emphasize the role of mTOR signalling in the pathogenesis of psoriasis, and support the investigation of topical mTOR inhibition as a novel anti-psoriatic strategy.
- Subjects :
- 0301 basic medicine
Administration, Topical
Neovascularization, Physiologic
Imiquimod
Dermatology
Pathogenesis
03 medical and health sciences
Immune system
Psoriasis
medicine
lcsh:Dermatology
Animals
Caspase 14
ddc:610
Protein Precursors
Mechanistic target of rapamycin
PI3K/AKT/mTOR pathway
Skin
Sirolimus
Mice, Inbred BALB C
Innate immune system
biology
business.industry
rapamycin
Macrophages
TOR Serine-Threonine Kinases
mTORC
RPTOR
Keratin-14
Membrane Proteins
General Medicine
Dendritic Cells
psoriasis
Keratin-10
lcsh:RL1-803
medicine.disease
3. Good health
imiquimod
Disease Models, Animal
030104 developmental biology
Ki-67 Antigen
Langerhans Cells
Cancer research
biology.protein
Aminoquinolines
Lymph Nodes
business
Immunosuppressive Agents
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 16512057 and 00015555
- Volume :
- 97
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Acta Dermato-Venereologica
- Accession number :
- edsair.doi.dedup.....90931a338480ed83b81231bc91e6c74e