TC-2559, an α4ß2 nicotinic acetylcholine receptor agonist, suppresses the expression of CCL3 and IL-1ß through STAT3 inhibition in cultured murine macrophages.

ABSTRACT

The anti-inflammatory properties of TC-2559, an α4ß2 nicotinic acetylcholine receptor (nAChR) agonist, on cultured murine macrophages was investigated. TC-2559 suppressed the upregulation of CC-chemokine ligand 3 (CCL3) and interleukin-1ß (IL-1ß) following lipopolysaccharide (LPS) treatment in J774A.1 cells. TC-2559 inhibited the phosphorylation of signal transducer and activator of transcription 3 (pSTAT3) but not nuclear factor-κB p65 after LPS. Blockade of pSTAT3 by AG490 inhibited the upregulation of CCL3 and IL-1ß after LPS. In conclusion, TC-2559-driven α4ß2 nAChR signaling suppressed the upregulation of CCL3 and IL-1ß by inhibiting pSTAT3 in inflammatory macrophages, resulting in the suppression of neuropathic pain.