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Modulation of intra-pulmonary TGF-b expression by mycophenolate mofetil in lupus prone MRL/lpr mice

Department of Medicine, Queen Mary Hospital, University of Hong Kong, Pokfulam, Hong Kong

J CK Leung

Department of Medicine, Queen Mary Hospital, University of Hong Kong, Pokfulam, Hong Kong

L YY Chan

Department of Medicine, Queen Mary Hospital, University of Hong Kong, Pokfulam, Hong Kong

S L Lui

Department of Medicine, Queen Mary Hospital, University of Hong Kong, Pokfulam, Hong Kong

A WL Tsang

Department of Medicine, Queen Mary Hospital, University of Hong Kong, Pokfulam, Hong Kong

K N Lai

Department of Medicine, Queen Mary Hospital, University of Hong Kong, Pokfulam, Hong Kong, knlai{at}hkucc.hku.hk

We investigated the expression profile of inflammatory cytokines in the lung of lupus-prone MRL/lpr mice and evaluated the therapeutic potential of mycophenolate mofetil (MMF) in reducing pulmonary cytokines in active lupus. Eight-week old female MRL/lpr mice (n = 20) were treated with MMF in vehicle by oral gavage. Disease control MRL/lpr mice (n = 30) or normal control MRL mice (n = 20) received vehicle alone. The mice were sacrificed after eight or 12 weeks of treatment. Gene expression and protein synthesis of IL-1ß, MCP-1 and TGF-ß1 in lung tissues were determined. We found an increase in the gene expression of IL-1ß, MCP-1 and TGF-ß1 in lung tissues of untreated MRL/lpr mice compared with MRL mice at either 16 weeks or 20 weeks of age. MMF treatment significantly prolonged the survival of MRL/lpr mice, down-regulated the gene expression of IL-1ß, MCP-1 and TGF-ß1 in lung tissues at the end of eight or 12 weeks of treatment. Protein synthesis of TGF-b1 was decreased following eight weeks of MMF treatment. We conclude that MMF treatment can reduce the TGF-b1 gene expression and protein synthesis in lung tissues of lupus-prone mice. Our findings provide experimental data suggesting a beneficial potential of MMF therapy in pulmonary involvement of lupus.

Key Words: cytokine • lung • MRL/lpr mice • mycophenolate mofetil • systemic lupus erythematosus • TGF-ß

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