Development of an inducible psoriasis-like in vivo model

Psoriasis is a common chronic inflammatory skin condition. Several key mediators have been identified to play a role in the pathogenesis of this disease including PPARd and STAT3. PPARd is a member of the Peroxisome Proliferator Activator Receptor family and has been implicated in psoriasis, as supported by microarray and immunohistochemical data. Based on these data, we sought to generate an in vivo model that overexpresses PPARd specifically in the epidermis. A model was available that we sought to characterise. This model, following induction with a specific PPARd ligand, results in a psoriasis-like skin phenotype, accompanied by immune system activation and gene dysregulation. In addition, STAT3 is highly activated in this animal model in the suprabasal layer of murine skin, which is an important feature of psoriasis. The inhibition of STAT3 inhibits phenotype development in this model. In addition, in this model, interferon response genes are downregulated, which contrasts with human psoriasis. However this downregulation is partially reversed following treatment with WP1066 as measured by the expression of IFI27, suggesting that activation of STAT3 is at least partially responsible for IFN target gene repression. This data show that epidermis-specific overexpression of PPARd results in a psoriasis-like phenotype, suggesting a central role for PPARd in psoriasis. STAT3 is also highly activated in this model, supporting the current evidence that STAT3 plays a role in psoriatic disease. Together, this suggests that STAT3 activation occurs downstream of PPARd activation and indicates that inhibition of PPARd may be effective for the treatment of psoriasis.

Name dc:type.qualificationname

Master of Science

Level dc:type.qualificationlevel

Master's Thesis

Grantor dc:publisher.institution

University of Dundee

Year dc:date.issued

2011

Author dc:creator

• Reilly, Louise

Advisor dc:contributor.advisor

• Foerster, John

• Psoriasis
• Skin
• In vivo

Language dc:language

eng

Identifier

oai:discovery.dundee.ac.uk:studenttheses/c5d38fdc-183d-45c4-b697-05e770d378f9

OAI identifier oai:identifier

oai:discovery.dundee.ac.uk:studenttheses/c5d38fdc-183d-45c4-b697-05e770d378f9