PMID- 10438961 OWN - NLM STAT- MEDLINE DCOM- 19990909 LR - 20081121 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 163 IP - 4 DP - 1999 Aug 15 TI - Differential monocyte chemoattractant protein-1 and chemokine receptor 2 expression by murine lung fibroblasts derived from Th1- and Th2-type pulmonary granuloma models. PG - 2193-201 AB - 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. FAU - Hogaboam, C M AU - Hogaboam CM AD - Department of Pathology, Division of Pulmonary and Critical Care, University of Michigan Medical School, Ann Arbor 48109, USA. hogaboam@path.med.umich.edu FAU - Bone-Larson, C L AU - Bone-Larson CL FAU - Lipinski, S AU - Lipinski S FAU - Lukacs, N W AU - Lukacs NW FAU - Chensue, S W AU - Chensue SW FAU - Strieter, R M AU - Strieter RM FAU - Kunkel, S L AU - Kunkel SL LA - eng GR - 1P50HL60289/HL/NHLBI NIH HHS/United States GR - HL35276/HL/NHLBI NIH HHS/United States GR - P01-HL31963/HL/NHLBI NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Ccr2 protein, mouse) RN - 0 (Chemokine CCL2) RN - 0 (Procollagen) RN - 0 (RNA, Messenger) RN - 0 (Receptors, CCR2) RN - 0 (Receptors, Chemokine) RN - 0 (Receptors, Cytokine) RN - 0 (Transforming Growth Factor beta) RN - 207137-56-2 (Interleukin-4) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Animals MH - Blotting, Western MH - Cells, Cultured MH - Chemokine CCL2/*biosynthesis/physiology MH - Disease Models, Animal MH - Female MH - Fibroblasts/*metabolism MH - Flow Cytometry MH - Gene Expression Regulation/immunology MH - Granuloma, Respiratory Tract/*immunology/metabolism MH - Interferon-gamma/pharmacology MH - Interleukin-4/pharmacology MH - Lung/cytology/*metabolism MH - Mice MH - Mice, Inbred CBA MH - Procollagen/biosynthesis/genetics MH - RNA, Messenger/drug effects/metabolism MH - Receptors, CCR2 MH - Receptors, Chemokine/*biosynthesis MH - Receptors, Cytokine/analysis/*biosynthesis/genetics MH - Th1 Cells/chemistry/*metabolism MH - Th2 Cells/chemistry/*metabolism MH - Transforming Growth Factor beta/biosynthesis EDAT- 1999/08/10 00:00 MHDA- 1999/08/10 00:01 CRDT- 1999/08/10 00:00 PHST- 1999/08/10 00:00 [pubmed] PHST- 1999/08/10 00:01 [medline] PHST- 1999/08/10 00:00 [entrez] AID - ji_v163n4p2193 [pii] PST - ppublish SO - J Immunol. 1999 Aug 15;163(4):2193-201.