Pharmacological Modulation of LPS-Induced MIP-1α Production by Peripheral Blood Mononuclear Cells

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Abstract
In the present study, we investigated the effects of some anti-asthmatic drugs on the production of the CC chemokine, macrophage inflammatory protein-1α (MIP-1α), in response to lipopolysaccharide (LPS) by peripheral blood mononuclear cells (PBMC). MIP-1α production was induced by LPS in a concentration-dependent fashion and reached the maximum at 10 µg/ml LPS (27.5±2.3 ng MIP-1α/106 PBMC). At a submaximal concentration of LPS (1 µg/ml), the release of MIP-1α increased with time and reached the maximum 24 h after LPS stimulation. Actinomycin D and cycloheximide inhibited MIP-1α production completely, but glucocorticoids did not completely inhibit MIP-1α production, with a maximum inhibition of 70%. We examined the effect of β-stimulants and phosphodiesterase inhibitors, which upregulate intracellular cyclic AMP levels, on MIP-1α production. When PBMC were treated with β-stimulants alone, β-stimulants showed a slightly inhibitory effect on MIP-1α production. However, the coadministration of roliplam significantly potentiated the inhibitory effect of β-stimulants on MIP-1α production. Moreover, db-cAMP suppressed MIP-1α production dose-dependently. The above data indicate that the production of MIP-1α is regulated by cyclic AMP and that cyclic AMP could provide a useful target for therapeutic treatment in asthmatic diseases and other diseases where MIP-1α is involved in their etiology.