Differential monocyte chemoattractant protein-1 and chemokine receptor 2 expression by murine lung fibroblasts derived from Th1-and Th2-type pulmonary granuloma models

Recent studies suggest that monocyte chemoattractant protein-1 (MCP-1) is i nvolved in fibrosis through the regulation of profibrotic cytokine generati on and matrix deposition. Changes in MCP-1, C-C chemokine receptor 2 (CCR2) , procollagen I and Iii, and TGF beta were examined in fibroblasts cultured from normal lung and from nonfibrotic (i.e., Th1-type) and fibrotic (i.e., Th2-type) pulmonary granulomas, Th2-type fibroblasts generated 2-fold more MCP-1 than similar numbers of Th1-type or normal fibroblasts after 24 h in culture. Unlike normal and Th1-type fibroblasts, Th2-type fibroblasts disp layed CCR2 mRNA at 24 h after IL-4 treatment. By flow cytometry, CCR2 was p resent on 40% of untreated Th2-type fibroblasts, whereas CCR2 was present o n <20% of normal and Th1-type fibroblasts after similar treatment. IL-4 inc reased the number of normal fibroblasts with cell-surface CCR2 but IFN-gamm a-treatment of normal and Th2-type fibroblasts significantly decreased the numbers of CCR2-positive cells in both populations. Western blot analysis s howed that total CCR2 protein expression was markedly increased in untreate d Th2-type fibroblasts compared with normal and Th1-type fibroblasts, IL-4 treatment enhanced CCR2 protein in Th1- and Th2-type fibroblasts whereas IF N-gamma treatment augmented CCR2 protein in normal and Th1-type fibroblasts . All three fibroblast populations exhibited MCP-1-dependent TGF-beta synth esis, but only normal and Th2-type fibroblasts showed a MCP-1 requirement f or procollagen mRNA expression. Taken together, these findings suggest that lung fibroblasts are altered in their expression of MCP-1, TGF-beta, CCR2, and procollagen following their participation in pulmonary inflammatory pr ocesses, and these changes may be important during fibrosis.