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α 1 ‐Adrenergic Receptor Modulation of LPS Induced Inflammation in Normal and PMA Differentiated THP‐1 Cells
Author(s) -
Grisanti Laurel A,
Porter James E
Publication year - 2009
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.23.1_supplement.941.1
Subject(s) - thp1 cell line , lipopolysaccharide , inflammation , population , immune system , monocyte , endocrinology , receptor , microbiology and biotechnology , phorbol , stimulation , medicine , chemistry , cytokine , proinflammatory cytokine , cell culture , biology , immunology , signal transduction , protein kinase c , genetics , environmental health
Catecholamines released from the sympathetic nervous system in response to stress or injury, impact expression of inflammatory cytokines generated by immune cells. Adrenergic receptors (AR) have been shown to be expressed on various immune cell populations, but have not been well characterized. A human monocytic cell line, THP‐1 and phorbol 12‐myristate 13‐acetate (PMA) differentiated THP‐1 cells were used to measure expression of an inflammatory mediator interleukin‐1β (IL‐1β) responding to α 1 ‐AR activation in the presence or absence of lipopolysaccharide (LPS). We hypothesized that stimulation of α 1 ‐ARs expressed on immune cells modulates IL‐1β production. Binding studies characterized a homogenous population of α 1 ‐ARs on THP‐1 cells, which changed to a heterogeneous population upon differentiation into macrophages. IL‐1β production in response to LPS was higher in the presence of α 1 ‐AR activation, which was also observed for macrophages. Increased p38 activation was seen with concurrent phenylephrine (PE) and LPS stimulation, which resulted in NF‐κB activational changes. Blocking p38 and PKC activation inhibited the synergistic increase in IL‐1β production observed with LPS and PE treatment. This study demonstrates that α 1 ‐ARs are present on both monocytic and monocyte derived macrophage cells and represents a mechanism by which innate immune responses can be modulated by adrenergic input. Funding: NSF Grant 0235146