Adrenaline inhibits lipopolysaccharide-induced macrophage inflammatory protein-1 alpha in human monocytes: the role of beta-adrenergic receptors.
Macrophage inflammatory protein-1 alpha (MIP-1 alpha) has an important role in the development of inflammatory responses during infection by regulating leukocyte trafficking and function. Our study was conducted to investigate the effect of adrenaline on lipopolysaccharide (LPS)-induced MIP-1 alpha production by human peripheral blood monocytes and human monocytic THP-1 cells. Monocytes were incubated in vitro with LPS for 4 h at 37 degrees C in the presence and absence of adrenaline and/or specific alpha- and beta-adrenergic receptor antagonists and agonists. The effects of adrenaline on MIP-1 alpha synthesis were studied at the protein level by using enzyme-linked immunosorbent assays and at the messenger RNA level by using reverse transcriptase-polymerase chain reaction. Adrenaline inhibited LPS-induced MIP-1 alpha production in a dose-dependent manner. The suppressive effect could be completely prevented by propranolol, but not by phentolamine. The specific beta-adrenergic agonist isoproterenol produced the same inhibitory effect on LPS-induced MIP-1 alpha production, whereas the alpha-adrenergic agonist phenylephrine had a minimal effect. In addition, suppression of MIP-1 alpha production was associated with an increase of intracellular cyclic adenosine monophosphate (cAMP) by the cell membrane-permeable cAMP analog dibutyryl-cAMP. Furthermore, we found that adrenaline inhibited LPS-induced MIP-1 alpha messenger RNA expression. These findings suggest that adrenaline can modulate MIP-1 alpha production in inflammatory diseases and sepsis.
Li
Chi-Yuan
CY
Department of Anesthesiology, Orthopedics, and. Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China. cyli@ndmctsgh.edu.tw
Chou
Tz-Chong
TC
Lee
Chian-Her
CH
Tsai
Chien-Sung
CS
Loh
Shih-Hurng
SH
Wong
Chih-Shung
CS
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D003994:Bucladesine / Q000494:pharmacology; D054407:Chemokine CCL4; D000242:Cyclic AMP / Q000378:metabolism; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000633:toxicity; D004837:Epinephrine / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis* / Q000235:genetics; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D054407:Chemokine CCL4; D004731:Endotoxins; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D003994:Bucladesine; C044101:endotoxin, Escherichia coli; D000242:Cyclic AMP; D004837:Epinephrine