Upregulation of Interleukin-13 and Its Receptor in a Murine Model of Bleomycin-Induced Scleroderma
| Autor: | Mariko Matsushita, Toshiyuki Yamamoto, Kiyoshi Nishioka |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Pathology
medicine.medical_specialty medicine.medical_treatment Immunology Bleomycin Skin Diseases Peripheral blood mononuclear cell Statistics Nonparametric Mice chemistry.chemical_compound Downregulation and upregulation Fibrosis Animals Immunology and Allergy Medicine RNA Messenger Receptor Mice Inbred C3H Interleukin-13 Scleroderma Systemic integumentary system Reverse Transcriptase Polymerase Chain Reaction business.industry Biopsy Needle Receptors Interleukin-13 Receptors Interleukin General Medicine Interleukin-13 receptor medicine.disease Immunohistochemistry Interleukin-13 Receptor alpha1 Subunit Specific Pathogen-Free Organisms Up-Regulation Disease Models Animal Cytokine chemistry Interleukin 13 Female Interleukin-4 business |
| Zdroj: | International Archives of Allergy and Immunology. 135:348-356 |
| ISSN: | 1423-0097 1018-2438 |
| DOI: | 10.1159/000082331 |
| Popis: | Background: Interleukin-13 (IL-13) has been implicated in the pathogenesis of fibrotic conditions. Previously, a murine model for scleroderma has been established by repeated local injections of bleomycin. This animal model enabled us to study local expression and production of IL-13 in skin lesions during disease progression. Methods: Dermal sclerosis (DSc) was induced by repeated subcutaneous injections of bleomycin (1 mg/ml) in C3H/HeJ mice. IL-13 and IL-4 expressions were examined by RT-PCR, ELISA and immunohistochemistry. Results: RT-PCR showed that both IL-4 and IL-13 mRNA levels in skin lesions were increased and peaked after 4 weeks of bleomycin treatment. Quantification by densitometry revealed up to 4.2- and 1.9-fold increases, respectively. Immunohistochemical localization showed in skin lesions expression of IL-13 on infiltrating inflammatory cells, including mononuclear cells and possibly mast cells, increased with DSc progression. IL-13 protein production was also significantly increased. In skin lesions, IL-13 receptor (IL-13R) α2 expression was augmented mainly in the infiltrating mononuclear cells after 4 weeks of bleomycin exposure. IL-13Rα2, but not IL-13Rα1, mRNA was upregulated in the whole skin after 4 weeks. On the contrary, mRNA expression of IL-13Rα1 and IL- 13Rα2 was significantly altered in the cultured fibroblasts derived from bleomycin-treated skin. Conclusion: These data demonstrate that in skin lesions levels of IL-13 as well as its receptor increase in parallel with DSc progression, suggesting that IL-13 promotes the progression of cutaneous fibrosis/sclerosis in the murine model of bleomycin-induced scleroderma. |
| Databáze: | OpenAIRE |
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