期刊
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
卷 284, 期 2, 页码 L342-L349出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajplung.00168.2002
关键词
lipid mediators; lung; chemokines; monocyte chemoattractant protein-1; CC chemokine receptor 2
资金
- NCI NIH HHS [R29 CA 79046] Funding Source: Medline
- NHLBI NIH HHS [P50 HL 60289, R01 HL 51082, P50 HL 56402] Funding Source: Medline
CC chemokine receptor 2 (CCR2) -/- mice are protected from experimental pulmonary fibrosis, a disease increasingly recognized as being mediated by dysfunctional interactions between epithelial cells and fibroblasts. We have sought to investigate the interactions between alveolar epithelial cells (AECs) and fibroblasts in these fibrosis-resistant (CCR2 -/-) and fibrosis-sensitive (CCR2 +/+) mice. AECs from CCR2 -/- mice suppress fibroblast proliferation more than AECs from CCR2 -/- mice (77 vs. 43%). Exogenous administration of the CCR2 ligand monocyte chemoattractant protein-1 (MCP-1) to the fibroblast-AEC cocultures reverses the suppression mediated by CCR2 -/- AECs but has no effect with CCR2 -/- AECs. MCP-1 regulates AEC function but not fibroblast function. AEC inhibition of fibroblast proliferation was mediated by a soluble, aspirin-sensitive factor. Accordingly, AECs from CCR2 -/- mice produce greater quantities of PGE(2) than do AECs from CCR2 +/+ mice, and MCP-1 inhibits AEC-derived PGE(2) synthesis. Diminished PGE(2) production by AECs results in enhanced fibroproliferation. Thus an important profibrotic mechanism of MCP-1/CCR2 interactions is to limit PGE(2) production in AECs after injury, thus promoting fibrogenesis.
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