Modulation of intra-pulmonary TGF-beta expression by mycophenolate mofetil in lupus prone MRL/lpr 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-1beta, MCP-1 and TGF-beta1 in lung tissues were determined. We found an increase in the gene expression of IL-1beta, MCP-1 and TGF-beta1 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-1beta, MCP-1 and TGF-beta1 in lung tissues at the end of eight or 12 weeks of treatment. Protein synthesis of TGF-beta1 was decreased following eight weeks of MMF treatment. We conclude that MMF treatment can reduce the TGF-beta1 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.
Guo
H
H
Department of Medicine, Queen Mary Hospital, University of Hong Kong, Pokfulam, Hong Kong.
Leung
J C K
JC
Chan
L Y Y
LY
Lui
S L
SL
Tsang
A W L
AW
Lai
K N
KN
D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000209:etiology / Q000378:metabolism*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D007166:Immunosuppressive Agents; D007375:Interleukin-1; D012333:RNA, Messenger; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D009173:Mycophenolic Acid