1. Differential effects of macrophage- and granulocyte-macrophage colony-stimulating factors on cytokine gene expression during rat alveolar macrophage differentiation into multinucleated giant cells (MGC): role for IL-6 in type 2 MGC formation
- Author
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Lemaire I, Yang H, Lafont V, Dornand J, therese commes, and Mf, Cantin
- Subjects
Male ,Base Sequence ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,Macrophage Colony-Stimulating Factor ,Immunology ,Gene Expression ,Granulocyte-Macrophage Colony-Stimulating Factor ,Cell Differentiation ,In Vitro Techniques ,Giant Cells ,Polymerase Chain Reaction ,Recombinant Proteins ,Rats ,Neutralization Tests ,Transforming Growth Factor beta ,Macrophages, Alveolar ,Animals ,Cytokines ,Immunology and Allergy ,RNA, Messenger ,Rats, Wistar ,DNA Primers ,Interleukin-1 - Abstract
Macrophage colony-stimulating factor (M-CSF) and granulocyte-macrophage (GM)-CSF stimulate the differentiation of rat alveolar macrophages (AM) into multinucleated giant cells (MGC) with distinct phenotypes (type 1 and type 2 MGC). In the present study, we analyzed the profile of cytokine gene expression induced respectively, by M-CSF and GM-CSF during rat AM differentiation using reverse transcription-PCR. Enhanced mRNA expression for IL-1alpha, TNF-alpha, and TGF-beta1 was observed 3 h after treatment with M-CSF (50 U/ml) or GM-CSF (50 U/ml). In contrast, IL-6 mRNA expression was increased by GM-CSF but not M-CSF. Kinetic analysis indicated that GM-CSF stimulated IL-6 expression early (1.5 h), with maximal effect observed at 24 h and up to 5 days thereafter. Increased mRNA levels for IL-6 were associated with higher IL-6 activity in the culture media of differentiating AM. IL-6 activity was stimulated 3 h after treatment with GM-CSF and increased with time (up to 5 days). Interestingly, addition of exogenous IL-6 (20-100 ng/ml) alone or in combination with GM-CSF to AM cultures increased slightly and selectively the formation of MGC with type 2 phenotype. Conversely, neutralization of endogenous IL-6 during AM differentiation into MGC inhibited significantly (up to 50%) the formation of type 2 MGC. These results suggest a role for IL-6 in the formation of type 2 MGC and provide some insights into the mechanisms of MGC formation and the processes that regulate it positively.
- Published
- 1996