Corticosteroid inhibition of macrophage inflammatory protein-1α in human monocytes and alveolar macrophages

N. Berkman, P. J. Jose, T. J. Williams, T. J. Schall, P. J. Barnes, K. F. Chung*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


One of the major inducible cytokines secreted by mononuclear phagocytes is macrophage inflammatory protein 1 (MIP-1), which consists of two homologous polypeptides, MIP-1α and MIP-1β. MIP-1α possesses chemotactic and stimulatory activities for lymphocytes, eosinophils, and monocytes and may play a role in various pulmonary inflammatory conditions. We investigated the expression and release of MIP-1α from human peripheral blood monocytes (PBM) and alveolar macrophages (AM) after stimulation with lipopolysaccharide (LPS), interleukin-1α (IL-1β), tumor necrosis factor-α, and interferon-γ and the inhibitory effects of corticosteroids. LPS and IL-1β only enhanced MIP-1α mRNA and protein in a dose- and time-dependent fashion. Dexamethasone (10-9 to 10-4 M) inhibited the basal and induced production and expression of MIP-1α. In PBM, dexamethasone (10-6 M) reduced LPS- and IL- 1β-stimulated production of MIP-1α protein by 50 and 63%, respectively, maximally at 24 h, whereas the inhibition of mRNA expression occurred maximally at 4 h. Similar trends were observed for AM. MIP-1α mRNA decay was only slightly decreased in the presence of dexamethasone. Inhibition of LPS- induced MIP-1α mRNA by dexamethasone was attenuated by the protein synthesis inhibitor cycloheximide, indicating the involvement of a protein intermediate. Corticosteroids are a potent inhibitor of IL-1β- and LPS- induced expression of MIP-1α through mechanisms involving mainly inhibition of transcription and to a minor degree by reducing mRNA stability. Corticosteroids may be effective anti-inflammatory agents by preventing the expression of chemokines such as MIP-1α.

Original languageAmerican English
Pages (from-to)L443-L452
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number4 13-4
StatePublished - 1995
Externally publishedYes


  • blood monocytes
  • chemokines


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