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Tumour necrosis factor-α plays a significant role in the Aldara-induced skin inflammation in mice.
Vinter, H; Kragballe, K; Steiniche, T; Gaestel, M; Iversen, L; Johansen, C.
Afiliação
  • Vinter H; Department of Dermatology, Aarhus University Hospital, P. P. Oerumsgade 11, Building 15B, DK-8000, Aarhus C, Denmark.
  • Kragballe K; Department of Dermatology, Aarhus University Hospital, P. P. Oerumsgade 11, Building 15B, DK-8000, Aarhus C, Denmark.
  • Steiniche T; Department of Pathology, Aarhus University Hospital, Tage Hansens Gade 2, DK-8000, Aarhus C, Denmark.
  • Gaestel M; Institute of Biochemistry, Hannover Medical University, 30625, Hannover, Germany.
  • Iversen L; Department of Dermatology, Aarhus University Hospital, P. P. Oerumsgade 11, Building 15B, DK-8000, Aarhus C, Denmark.
  • Johansen C; Department of Dermatology, Aarhus University Hospital, P. P. Oerumsgade 11, Building 15B, DK-8000, Aarhus C, Denmark.
Br J Dermatol ; 174(5): 1011-21, 2016 May.
Article em En | MEDLINE | ID: mdl-26614407
ABSTRACT

BACKGROUND:

Recently, the Aldara-induced psoriasis-like skin inflammation model in mice has attracted increased attention, due to its dependence on the same immunological pathways and cell types as in human psoriasis.

OBJECTIVES:

To study the impact of constitutive deficiency of tumour necrosis factor (TNF)-α and its upstream regulator mitogen-activated protein kinase-activated protein kinase 2 (MAPKAPK-2, herein MK2) in the Aldara-induced psoriasis-like skin inflammation model.

METHODS:

TNF-α knockout (KO), MK2 KO and wild-type (WT) mice divided into separate groups received either 45-mg Aldara cream or control cream for 5 consecutive days. The skin inflammation was evaluated clinically, histologically, and by quantitative reverse transcription-polymerase chain reaction.

RESULTS:

We found that TNF-α KO mice developed significantly less skin inflammation compared with WT mice, as evaluated clinically and histologically. At the molecular level, we demonstrated that the Aldara-induced mRNA expression of the psoriasis-related inflammatory markers interleukin (IL)-17C, IL-23p19, IL-12p40, IL-17A, IL-22 and S100A8 was significantly decreased in TNF-α KO mice compared with WT mice. No significant difference in the mRNA expression of these inflammatory markers between MK2 KO mice and WT mice was found, although Aldara-treated MK2 KO mice showed a tendency towards a lower mRNA expression of IL-17A and IL-22 compared with WT mice.

CONCLUSIONS:

We were able to demonstrate significantly lower levels of inflammation in TNF-α KO mice compared with WT mice, supporting the use of this model in future studies characterizing the role of TNF-α in psoriasis.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Psoríase / Adjuvantes Imunológicos / Fator de Necrose Tumoral alfa / Aminoquinolinas Idioma: En Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Psoríase / Adjuvantes Imunológicos / Fator de Necrose Tumoral alfa / Aminoquinolinas Idioma: En Ano de publicação: 2016 Tipo de documento: Article