Expression and regulation of human pulmonary fibroblast-derived monocyte chemotactic peptide-1.
Monocyte recruitment is essential for maintenance of normal pulmonary macrophage populations. In addition, acute and chronic inflammatory pulmonary diseases are associated with sequestration of mononuclear phagocytes in the lung. Although alveolar macrophages (AM phi) can secrete a number of potent inflammatory and chemoattractment mediators, these immune cells do not produce monocyte chemotactic peptide (MCP-1) in response to lipopolysaccharide (LPS), tumor necrosis factor (TNF), or interleukin-1 beta (IL-1 beta). The pulmonary fibroblast (PF) may play a pivotal role in monocyte recruitment. In these studies, we demonstrate a time- and dose-dependent production of PF-derived steady-state MCP-1 mRNA, MCP-1 antigen, and monocyte chemotactic bioactivity attributable to MCP-1. In cellular models examining cytokine networks between AM phi and PF, LSP-stimulated AM phi (conditioned media) induced PF-derived steady-state MCP-1 mRNA expression that was markedly attenuated by the presence of neutralizing TNF and IL-1 beta antibodies. Furthermore, we showed the dose- and time-dependent suppression of IL-1 beta-stimulated PF-derived MCP-1 by dexamethasone and prostaglandin E2. These findings demonstrated that PF are an important cellular source of MCP-1 and this production of MCP-1 may be influenced by immunomodulators.
Rolfe
M W
MW
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0360.
Kunkel
S L
SL
Standiford
T J
TJ
Orringer
M B
MB
Phan
S H
SH
Evanoff
H L
HL
Burdick
M D
MD
Strieter
R M
RM
D000906:Antibodies / Q000276:immunology; D001483:Base Sequence; D018932:Chemokine CCL2; D002630:Chemotactic Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D015232:Dinoprostone / Q000494:pharmacology*; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D000906:Antibodies; D018932:Chemokine CCL2; D002630:Chemotactic Factors; D007375:Interleukin-1; D015335:Molecular Probes; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D015232:Dinoprostone