Inflammatory Skin Disease in K5.hTGF-β1 Transgenic Mice Is Not Dependent on the IL-23/Th17 Inflammatory Pathway
| Autor: | Stephen E. Kurtz, Jacqueline M. Benson, David J. Hinrichs, Erin Fitch, Wei Gao, Andrew Blauvelt, Heather L. Rizzo, Keith W. Wegmann |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
Transgene
Inflammation Mice Transgenic Dermatology Biology Biochemistry Interleukin-23 Article Transforming Growth Factor beta1 030207 dermatology & venereal diseases 03 medical and health sciences Mice 0302 clinical medicine Psoriasis Interleukin 23 medicine Animals RNA Messenger Molecular Biology Interleukin 4 Cells Cultured 030304 developmental biology 0303 health sciences Experimental autoimmune encephalomyelitis Interleukin-17 Antibodies Monoclonal Cell Biology T-Lymphocytes Helper-Inducer Immunoglobulin E medicine.disease Interleukin-12 3. Good health Disease Models Animal Immunology Interleukin 12 Interleukin 17 Interleukin-4 medicine.symptom Signal Transduction |
| Zdroj: | Journal of Investigative Dermatology |
| ISSN: | 0022-202X |
| DOI: | 10.1038/jid.2009.88 |
| Popis: | In the presence of IL-6, transforming growth factor (TGF)-beta1 induces differentiation of T helper (Th) 17 cells in mice. Interleukin (IL)-23, a heterodimeric cytokine composed of IL-23p19 and IL-12/23p40 subunits, stimulates the growth and expansion of Th17 cells, and has been implicated in psoriasis pathogenesis. To study the associations between TGF-beta1, the IL-23/Th17 inflammatory pathway, and psoriasis, we investigated inflammatory skin disease in transgenic mice that constitutively overexpress human TGF-beta1 in basal keratinocytes (K5.hTGF-beta1 transgenic mice); these mice had previously been reported as having a psoriasis-like disease. K5.hTGF-beta1 transgenic mice had high levels of TGF-beta1 mRNA and protein in both skin and serum. Levels of cytokines involved in IL-23/Th17-mediated inflammation were not elevated in lesional skin compared with those in non-lesional and wild-type skin. It is noteworthy that IL-4 and IgE were markedly elevated in inflamed skin and serum, respectively, of transgenic mice. Monoclonal antibodies (mAbs) specifically directed against IL-23p19 or IL-12/23p40 had no clinical effect on established inflammatory skin disease in K5.hTGF-beta1 transgenic mice, whereas the same mAbs were able to block the development of murine experimental autoimmune encephalomyelitis, an IL-23/Th17-mediated disease. In summary, the IL-23/Th17 inflammatory pathway is not responsible for the maintenance of inflammatory skin disease in K5.hTGF-beta1 transgenic mice. |
| Databáze: | OpenAIRE |
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