Upregulation of interleukin-13 and its receptor in a murine model of bleomycin-induced scleroderma.
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) alpha2 expression was augmented mainly in the infiltrating mononuclear cells after 4 weeks of bleomycin exposure. IL-13Ralpha2, but not IL-13Ralpha1, mRNA was upregulated in the whole skin after 4 weeks. On the contrary, mRNA expression of IL-13Ralpha1 and IL- 13Ralpha2 was significantly altered in the cultured fibroblasts derived from bleomycin-treated skin.


CONCLUSIONS
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.
Matsushita
Mariko
M
Department of Dermatology, Tokyo Medical and Dental University, School of Medicine, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan. mariko.derm@tmd.ac.jp
Yamamoto
Toshiyuki
T
Nishioka
Kiyoshi
K
D000818:Animals; D001707:Biopsy, Needle; D001761:Bleomycin; D004195:Disease Models, Animal; D005260:Female; D007150:Immunohistochemistry; D018793:Interleukin-13 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D053661:Interleukin-13 Receptor alpha1 Subunit; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018123:Receptors, Interleukin / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D053660:Receptors, Interleukin-13; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012595:Scleroderma, Systemic / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D012871:Skin Diseases / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D013047:Specific Pathogen-Free Organisms; D018709:Statistics, Nonparametric; D015854:Up-Regulation / Q000276:immunology
C508183:Il13ra1 protein, mouse; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D001761:Bleomycin; D015847:Interleukin-4