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Bürger, C; Shirsath, N; Lang, V; Diehl, S; Kaufmann, R; Weigert, A; Han, YY; Ringel, C; Wolf, P.
Blocking mTOR Signalling with Rapamycin Ameliorates Imiquimod-induced Psoriasis in Mice.
Acta Derm Venereol. 2017; 97(9):1087-1094 [OPEN ACCESS]
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Autor/innen der Med Uni Graz:
Shirsath Nitesh Pralhad
Wolf Peter
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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.
Find related publications in this database (using NLM MeSH Indexing)
Administration, Topical -
Aminoquinolines - adverse effects
Animals -
Caspase 14 - metabolism
Dendritic Cells - metabolism
Disease Models, Animal -
Imiquimod -
Immunosuppressive Agents - pharmacology
Keratin-10 - metabolism
Keratin-14 - metabolism
Ki-67 Antigen - metabolism
Langerhans Cells - metabolism
Lymph Nodes - metabolism
Macrophages - metabolism
Membrane Proteins - metabolism
Mice, Inbred BALB C -
Neovascularization, Physiologic - drug effects
Protein Precursors - metabolism
Psoriasis - chemically induced
Psoriasis - drug therapy
Sirolimus - pharmacology
Skin - metabolism
TOR Serine-Threonine Kinases - antagonists & inhibitors

Find related publications in this database (Keywords)
psoriasis
imiquimod
rapamycin
mTORC
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