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Synergistic α1‐adrenergic receptor mediated increases in IL‐1β from lipopolysaccharide‐challenged human monocytes is β‐arrestin 1‐dependent and NF‐κB‐independent
Author(s) -
Grisanti Laurel A,
Porter James E
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.586.4
Subject(s) - lipopolysaccharide , p38 mitogen activated protein kinases , nf κb , microbiology and biotechnology , innate immune system , chemistry , stimulation , receptor , mapk/erk pathway , signal transduction , arrestin , immune system , transcription factor , biology , immunology , endocrinology , g protein coupled receptor , biochemistry , gene
Adrenergic receptors (AR) are expressed on immune cell populations, but their precise function is not well characterized. We previously demonstrated that activation of α 1b ‐ARs synergistically increases IL‐1β release from lipopolysaccharide (LPS) challenged human monocytes through a PKC/p38 MAPK dependent mechanism. Studies show βarrestin signaling complexes regulate LPS induced NFκB activity as well as AR mediated p38 MAPK activation. Thus, we hypothesized that α 1b ‐ARs increases IL‐1β production from LPS‐primed monocytes through βarrestin enhancement of NFκB signaling. RNA interference demonstrated βarrestin 1 expression is needed for potentiated IL‐1β release from monocytes treated with phenylephrine (PE) and LPS. Using an NFκB inhibitor, we found a requirement for NFκB activation to increase IL‐1β production in cells treated with LPS alone. However, synergistic increases in IL‐1β from monocytes treated with PE and LPS are NFκB independent. Electrophoretic mobility shift and luciferase reporter assays showed NFκB protein/promoter interactions are disrupted, resulting in decreased transcription. Examination of alternative transcription factors demonstrated increased AP‐1 activation. These results provide evidence for a novel βarrestin 1 dependent, NFκB independent mechanism through which α 1b ‐AR stimulation potentiates the innate immune response from LPS challenged human monocytes.