Inhibition of monocyte chemoattractant protein-1 expression in cytokine-treated human lung epithelial cells by thiazolidinedione.
OBJECTIVE
Several lung diseases are characterized by the presence of increased numbers of activated macrophages. The recruitment and activation of peripheral blood monocytes are potentially critical regulatory events for the control of pulmonary inflammation. The chemokine monocyte chemoattractant protein (MCP)-1 is a potent chemoattractant for monocytes. MCP-1 is produced by lung epithelial cells during the course of inflammatory lung diseases. In the present study, we examined the effects of a thiazolidinedione (TZD), which is used to improve the insulin resistance of individuals with diabetes mellitus, on MCP-1 expression in a human lung epithelial cell line, A549.


RESULTS
In A549 cells, interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha induced endogenous MCP-1 protein secretion and messenger RNA expression. The TZD inhibited the increase of MCP-1 secretion by IL-1beta and TNF-alpha treatment. The TZD inhibited the expression of MCP-1 messenger RNA with IL-1beta treatment, but not with TNF-alpha treatment. This observation was confirmed by the results of a monocyte chemotactic assay. The transcriptional activity of human MCP-1 promoter in A549 cells paralleled the endogenous messenger RNA expression by cytokines and TZD treatment.


CONCLUSIONS
Our findings indicated that the suppression of the expression of MCP-1 could be accomplished by TZD treatment, raising the possibility that TZD may be of therapeutic value in several lung diseases in which MCP-1 plays an important role.
Momoi
A
A
First Department of Internal Medicine, Kagawa Medical University, Kita-gun, Kagawa, Japan.
Murao
K
K
Imachi
H
H
Ishida
T
T
Cao
W M
WM
Sato
M
M
Takahara
J
J
D000230:Adenocarcinoma; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors* / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects*; D008175:Lung Neoplasms; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D020545:Respiratory Mucosa / Q000187:drug effects; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D018932:Chemokine CCL2; D007375:Interleukin-1; D012333:RNA, Messenger; D013844:Thiazoles; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; C089946:2,4-thiazolidinedione