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Inflammasome activation: A form of autocrine purinergic signaling in monocytes
Author(s) -
Lee Albert,
Staudenmaier Laura,
Li Xiaoou,
Zhang Jingping,
Junger Wolfgang
Publication year - 2015
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.29.1_supplement.973.5
Subject(s) - autocrine signalling , purinergic receptor , inflammasome , purinergic signalling , microbiology and biotechnology , lipopolysaccharide , signal transduction , suramin , paracrine signalling , receptor , biology , chemistry , pharmacology , immunology , extracellular , biochemistry , adenosine receptor , agonist
Previously, we have demonstrated that autocrine purinergic signaling plays an important role in host defense. ATP is released from immune cells including neutrophils and T cells upon pathogen recognition. Released ATP triggers autocrine feedback signaling via purinergic receptors that regulate cell functions such as chemotaxis and T cell proliferation. Here, we studied whether inflammasome activation in monocytes involves similar autocrine purinergic signaling mechanisms. We found that toll‐like receptor (TLR) stimulation of human monocytes causes the release of ATP, which could be blocked with the gap junction inhibitor carbenoxolone (CBX) (Fig. 1A). Inhibition of ATP release with CBX or interruption of autocrine purinergic feedback with suramin, a non‐specific P2 receptor antagonist, dose‐dependently blocked TLR‐induced IL‐1β expression by lipopolysaccharide (LPS) stimulated monocytes (Fig. 1B). We conclude that inflammasome activation in response to TLR stimulation involves autocrine purinergic signaling systems similar to those previously defined in neutrophils and T cells. This study was supported by NIH grants R01 GM51477, R01 GM60475, R01 AI080582, and T32 GM103702. Fig. 1 A. Human monocytes were stimulated with LPS (500 pg/ml), in the presence or absence of CBX (100 µM) and ATP release was measured with a luciferase assay. B. Monocytes were pre‐treated for 20 min with suramin, stimulated with LPS (500 pg/ml), and IL‐1β expression measured by ELISA after 24 h. Student's t‐test, * p<0.05; 蠅3 independent experiments.