Modulation of intra-pulmonary TGF-β expression by mycophenolate mofetil in lupus prone MRL/1pr mice

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- 1 beta, MCP- 1 and TGF- beta 1 in lung tissues were etermined. We found an increase in the gene expression of IL- 1 beta, MCP- 1 and TGF- beta 1 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- 1 beta, MCP- 1 and TGF- beta 1 in lung tissues at the end of eight or 12 weeks of treatment. Protein synthesis of TGF-beta 1 was decreased following eight weeks of MMF treatment. We conclude that MMF treatment can reduce the TGF-beta 1 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.