Inhibition of macrophage inflammatory protein-1α expression by IL-10: Differential sensitivities in human blood monocytes and alveolar macrophages

N. Berkman, M. John, G. Roesems, P. J. Jose, P. J. Barnes, K. F. Chung*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

133 Scopus citations

Abstract

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-1α (MIP-1α), which is a potent chemoattractant for activated T cells, we studied the effects of IL-10 on the expression of MIP- 1α in these cells. Low levels of MIP-1α were detectable in resting monocytes and macrophages. Both LPS (1 μg/ml) and IL-1β (10 ng/ml) induced the expression of MIP-1α mRNA and the release of MIP-1α protein from these cells. The addition of exogenous human rIL-10 inhibited induced MIP-1α mRNA expression as well as the release of MIP-1α protein measured after 24 h. This inhibition was significantly higher in monocytes compared with alveolar macrophages. In monocytes, IL-10-induced inhibition of MIP-1α 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-1α induced by LPS and IL-1β was further enhanced in monocytes but unchanged in alveolar macrophages. MIP-1α mRNA was also increased in monocytes. There was no detectable release of IL-10 from alveolar macrophages after LPS or IL-1β in contrast to modest amounts released from monocytes. Thus, IL-10 is an inhibitor of the induced transcription of MIP-1α mRNA and of the release of MIP-1α 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-1α expression from monocytes and macrophages.

Original languageAmerican English
Pages (from-to)4412-4418
Number of pages7
JournalJournal of Immunology
Volume155
Issue number9
StatePublished - 1995
Externally publishedYes

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