TGFΒ1 OVEREXPRESSION IN BASAL KERATINOCYTES CAUSES UPREGULATION OF S100A8, S100A9 AND INFILTRATION OF MPO+ CELLS WITHIN THE SKIN
Open Access
Author:
Koubek, Richard Donovan
Area of Honors:
Immunology and Infectious Disease
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
Adam Bleier Glick, Thesis Supervisor Adam Bleier Glick, Thesis Supervisor James Endres Howell, Thesis Honors Advisor
Keywords:
TGFΒ1 KERATINOCYTES S100A8 S100A9 MPO
Abstract:
Transforming growth factor beta1 (TGFβ1) is a ubiquitous cytokine made by most cell types in the body. However, the effects of TGFβ1 are both diverse and largely context dependent. Overexpression of TGFβ1 has also been shown to cause hyperproliferative type disorders, with implications for cancer promotion through supporting chronic inflammation. Therefore, this study seeks to further understand the effect of TGFβ1 overexpression on skin condition and proliferation within both normal and inflamed skin. Utilizing a transgenic mouse model, TGFβ1 expression was induced at the keratin-5 promotor in the basal layer of the epidermis. Expression was induced for acute (five day) and chronic (two week) periods in both normal and inflamed, TPA-treated, skin. Through this experimentation, it was found that overexpression of TGFβ is able to induce increased levels of S100A8 and S100A9, MPO+ cell recruitment to the epidermis, and epidermal thickness in both normal and chronically inflamed skin. These effects could be seen after only four days of TGFβ induction, and were amplified over time in normal skin. However, the exact mechanism of S100A8 and S100A9 upregulation remains unclear.
