Inhibition of macrophage inflammatory protein-1 alpha expression by IL-10. Differential sensitivities in human blood monocytes and alveolar macrophages.
IL-10 is a pleiotropic cytokine produced by monocytes and T cells that has potent inhibitory effects on monocyte/macrophage function. Because monocytes and macrophages are capable of releasing the C-C chemokine, macrophage inflammatory protein-1 alpha (MIP-1 alpha), which is a potent chemoattractant for activated T cells, we studied the effects of IL-10 on the expression of MIP-1 alpha in these cells. Low levels of MIP-1 alpha were detectable in resting monocytes and macrophages. Both LPS (1 micrograms/ml) and IL-1 beta (10 ng/ml) induced the expression of MIP-1 alpha mRNA and the release of MIP-1 alpha protein from these cells. The addition of exogenous human rIL-10 inhibited induced MIP-1 alpha mRNA expression as well as the release of MIP-1 alpha protein measured after 24 h. This inhibition was significantly higher in monocytes compared with alveolar macrophages. In monocytes, IL-10-induced inhibition of MIP-1 alpha was only partially accounted for by alterations in mRNA stability and was dependent on de novo protein synthesis. In the presence of an anti-human IL-10-neutralizing Ab, the release of MIP-1 alpha induced by LPS and IL-1 beta was further enhanced in monocytes but unchanged in alveolar macrophages. MIP-1 alpha mRNA was also increased in monocytes. There was no detectable release of IL-10 from alveolar macrophages after LPS or IL-1 beta in contrast to modest amounts released from monocytes. Thus, IL-10 is an inhibitor of the induced transcription of MIP-1 alpha mRNA and of the release of MIP-1 alpha protein, with a greater effect on monocytes as compared with alveolar macrophages. IL-10 may indirectly regulate effects on cells such as activated T lymphocytes partly through the inhibition of MIP-1 alpha expression from monocytes and macrophages.
Berkman
N
N
Department of Thoracic Medicine, National Heart and Lung Institute, London, United Kingdom.
John
M
M
Roesems
G
G
Jose
P J
PJ
Barnes
P J
PJ
Chung
K F
KF
D000906:Antibodies / Q000494:pharmacology; D001667:Binding, Competitive; D054407:Chemokine CCL4; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D019402:Macrophage Inflammatory Proteins; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D015846:Monokines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects
D000906:Antibodies; D054407:Chemokine CCL4; D016207:Cytokines; D007166:Immunosuppressive Agents; D007375:Interleukin-1; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D016753:Interleukin-10