Stimulation of adenosine A2A receptor inhibits LPS-induced expression of intercellular adhesion molecule 1 and production of TNF-alpha in human peripheral blood mononuclear cells

Ryosuke Hamano; Hideo Kohka Takahashi; Hiromi Iwagaki; Toru Kanke; Keyue Liu; Tadashi Yoshino; Toshiaki Sendo; Masahiro Nishibori; Noriaki Tanaka

doi:10.1097/shk.0b013e31812385da

Stimulation of adenosine A2A receptor inhibits LPS-induced expression of intercellular adhesion molecule 1 and production of TNF-alpha in human peripheral blood mononuclear cells

Shock. 2008 Feb;29(2):154-9. doi: 10.1097/shk.0b013e31812385da.

Authors

Ryosuke Hamano¹, Hideo Kohka Takahashi, Hiromi Iwagaki, Toru Kanke, Keyue Liu, Tadashi Yoshino, Toshiaki Sendo, Masahiro Nishibori, Noriaki Tanaka

Affiliation

¹ Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Shikata-cho, Okayama, Japan.

PMID: 17693933
DOI: 10.1097/shk.0b013e31812385da

Abstract

LPS stimulates CD14/Toll-like receptor (TLR) 4, leading to induce TNF-alpha production. Cell-to-cell interaction through the engagement between intercellular adhesion molecule (ICAM) 1 on monocytes and its ligand on T cells has been suggested to play a role in the TNF-alpha production by LPS-treated human peripheral blood mononuclear cells (PBMCs). Adenosine is reported to inhibit LPS-induced TNF-alpha production. However, little is known about the mechanism of the inhibitory effects induced by adenosine on the LPS-induced immune responses. We found that adenosine inhibited the expression of ICAM-1 and the production of TNF-alpha by human PBMC via adenosine A2A receptor in the presence of LPS. However, the stimulation of A1R or A3R enhanced the actions of adenosine. Adenosine had no effect on the expression of CD14 and TLR-4, suggesting that the inhibitory effects of adenosine on the LPS actions might be independent of the expression of CD14 and TLR-4. Thus, adenosine differentially regulates the expression of ICAM-1 and the production of TNF-alpha through plural subtypes of receptors.

MeSH terms

Adenosine / pharmacology
Adenosine A1 Receptor Agonists
Adenosine A1 Receptor Antagonists
Adenosine A2 Receptor Agonists
Adenosine A2 Receptor Antagonists
Adenosine A3 Receptor Agonists
Adenosine A3 Receptor Antagonists
CD40 Antigens / metabolism
Cells, Cultured
Cyclic AMP / metabolism
Enzyme-Linked Immunosorbent Assay
Flavins / pharmacology
Flow Cytometry
Humans
Intercellular Adhesion Molecule-1 / metabolism*
Leukocytes, Mononuclear / drug effects*
Leukocytes, Mononuclear / metabolism
Lipopolysaccharide Receptors / metabolism
Lipopolysaccharides / pharmacology*
Receptor, Adenosine A2A / physiology*
Triazines / pharmacology
Triazoles / pharmacology
Tumor Necrosis Factor-alpha / metabolism*
Xanthines / pharmacology

Substances

Adenosine A1 Receptor Agonists
Adenosine A1 Receptor Antagonists
Adenosine A2 Receptor Agonists
Adenosine A2 Receptor Antagonists
Adenosine A3 Receptor Agonists
Adenosine A3 Receptor Antagonists
CD40 Antigens
Flavins
Lipopolysaccharide Receptors
Lipopolysaccharides
Receptor, Adenosine A2A
Triazines
Triazoles
Tumor Necrosis Factor-alpha
Xanthines
ZM 241385
Intercellular Adhesion Molecule-1
isoalloxazine
1,3-dipropyl-8-cyclopentylxanthine
Cyclic AMP
Adenosine