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 involved in fibrosis through the regulation of profibrotic cytokine generation 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 displayed CCR2 mRNA at 24 h after IL-4 treatment. By flow cytometry, CCR2 was present on 40% of untreated Th2-type fibroblasts, whereas CCR2 was present on <20% of normal and Th1-type fibroblasts after similar treatment. IL-4 increased the number of normal fibroblasts with cell-surface CCR2 but IFN-gamma-treatment of normal and Th2-type fibroblasts significantly decreased the numbers of CCR2-positive cells in both populations. Western blot analysis showed that total CCR2 protein expression was markedly increased in untreated Th2-type fibroblasts compared with normal and Th1-type fibroblasts. IL-4 treatment enhanced CCR2 protein in Th1- and Th2-type fibroblasts whereas IFN-gamma treatment augmented CCR2 protein in normal and Th1-type fibroblasts. All three fibroblast populations exhibited MCP-1-dependent TGF-beta synthesis, but only normal and Th2-type fibroblasts showed a MCP-1 requirement for 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 processes, and these changes may be important during fibrosis.
Hogaboam
C M
CM
Department of Pathology, Division of Pulmonary and Critical Care, University of Michigan Medical School, Ann Arbor 48109, USA. hogaboam@path.med.umich.edu
Bone-Larson
C L
CL
Lipinski
S
S
Lukacs
N W
NW
Chensue
S W
SW
Strieter
R M
RM
Kunkel
S L
SL
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology; D015769:Granuloma, Respiratory Tract / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008808:Mice, Inbred CBA; D011347:Procollagen / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000096:biosynthesis*; D018121:Receptors, Cytokine / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D018417:Th1 Cells / Q000737:chemistry / Q000378:metabolism*; D018418:Th2 Cells / Q000737:chemistry / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D011347:Procollagen; D012333:RNA, Messenger; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D007371:Interferon-gamma