Corticosteroid inhibition of macrophage inflammatory protein
-1[alpha] expression in human monocytes and alveolar macrophages.
Berkman, N., P. J. Jose, T. J. Williams, P. J. Barnes, K. F. Chung.
Department of Thoracic Medicine & Applied Pharmacology, National
Heart & Lung Institute, London SW3, UK
APStracts 2:0086L, 1995.
One of the major inducible cytokines secreted by mononuclear
phagocytes is macrophage inflammatory protein 1 (MIP-1), which
consists of 2 homologous polypeptides, MIP-1[alpha] and MIP-1[beta].
MIP-1[alpha] 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-1[alpha] from human peripheral blood monocytes (PBM)
and alveolar macrophages (AM) following stimulation with
lipopolysaccharide (LPS), interleukin-1[beta] (IL-1[beta]), tumor
necrosis factor-[alpha] (TNF-[alpha]) and interferon-[tau] (IFN
-[tau]) and the inhibitory effects of corticosteroids. LPS and IL
-1[beta] only enhanced MIP-1[alpha] 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-1[alpha]. In PBM,
dexamethasone (10-6 M) reduced LPS- and IL-1[beta]-stimulated
production of MIP-1[alpha] protein by 50% and 63% respectively
maximally at 24 hours, while the inhibition of mRNA expression
occurred maximally at 4 hours. Similar trends were observed for AM.
MIP-1[alpha] mRNA decay was only slightly decreased in the presence
of dexamethasone. Inhibition of LPS-induced MIP-1[alpha] 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-1[beta]- and LPS-induced
expression MIP-1[alpha] through mechanisms involving mainly
inhibition of transcription and to a minor degree by reducing mRNA
stability. Corticosteroids may be effective antiinflammatory agents
by preventing the expression of chemokines such as MIP-1[alpha].
Received 13 September 1994; accepted in final form 27 April 195.
APS Manuscript Number L273-4.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 26 May 1995.