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Exogenous and endogenous catecholamines inhibit the production of macrophage inflammatory protein (MIP) 1 α via a β adrenoceptor mediated mechanism
Author(s) -
Haskó György,
Shanley Thomas P,
Egnaczyk Greg,
Németh Zoltán H,
Salzman Andrew L,
Vizi E Sylvester,
Szabó Csaba
Publication year - 1998
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0702179
Subject(s) - rolipram , endocrinology , medicine , chemistry , zaprinast , agonist , phosphodiesterase inhibitor , prazosin , adenosine , propranolol , phentolamine , pharmacology , phosphodiesterase , antagonist , receptor , biology , biochemistry , enzyme
1 Noradrenaline (NA) and adrenaline (Ad) are modulators of cytokine production. Here we investigated the role of these neurotransmitters in the regulation of macrophage inflammatory protein (MIP)‐1α expression. 2 Pretreatment of RAW 264.7 macrophages with NA or Ad decreased, in a concentration‐dependent manner (1 n m –100 μ m ), MIP‐1α release induced by bacterial lipopolysaccharide (LPS 10 ng ml −1 LPS). The effect of NA was reversed by the selective β‐adrenoceptor antagonist propranolol (10 μ m ), but not by the α‐adrenoceptor antagonist phentolamine (10 μ m ). 3 In the concentration range of 10 n m –10 μ m , isoproterenol, a β‐adrenoceptor agonist, but not phenylephrine (a selective α 1 ‐adrenoceptor agonist) or UK‐14304 (a selective α 2 ‐adrenoceptor agonist) mimicked the inhibitory effects of catecholamines on MIP‐1α production. Increases in intracellular cyclic adenosine monophosphate, elicited either by the selective type IV phosphodiesterase inhibitor rolipram (0.1–10 μ m ), or by prostaglandin E 2 , (10 n m –10 μ m ) decreased MIP‐1α release, suggesting that increased cyclic AMP may contribute to the suppression of MIP‐1α release by β‐adrenoceptor stimulation. 4 Northern blot analysis demonstrated that NA (100 n m –10 μ m ), Ad, isoproterenol, as well as rolipram (100 n m –10 μ m ) decreased LPS‐induced MIP‐1α mRNA accumulation. NA and Ad (1–100 μ m ) also decreased MIP‐1α production in thioglycollate‐elicited murine peritoneal macrophages. 5 Pretreatment of mice with either isoproterenol (10 mg kg −1 , i.p.) or rolipram (25 mg kg −1 , i.p.) decreased LPS‐induced plasma levels of MIP‐1α, while propranolol (10 mg kg −1 , i.p.) augmented the production of this chemokine, confirming the role of a β‐adrenoceptor mediated endogenous catecholamine action in the regulation of MIP‐1α production in vivo . 6 Thus, based on our data we conclude that catecholamines are important endogenous regulators of MIP‐1α expression in inflammation.British Journal of Pharmacology (1998) 125 , 1297–1303; doi: 10.1038/sj.bjp.0702179