title: TC-2559, an α4β2 nicotinic acetylcholine receptor agonist, suppresses the expression of CCL3 and IL-1β through STAT3 inhibition in cultured murine macrophages.
abstract: The anti-inflammatory properties of TC-2559, an α4β2 nicotinic acetylcholine receptor (nAChR) agonist, on cultured murine macrophages was investigated. TC-2559 suppressed the upregulation of CC-chemokine ligand 3 (CCL3) and interleukin-1β (IL-1β) 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-1β after LPS. In conclusion, TC-2559-driven α4β2 nAChR signaling suppressed the upregulation of CCL3 and IL-1β by inhibiting pSTAT3 in inflammatory macrophages, resulting in the suppression of neuropathic pain.
authors.affiliation: Department of Pharmacology, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-0012, Japan; Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA.
authors.forename: Norikazu
authors.initials: N
authors.lastname: Kiguchi
authors.affiliation: Department of Pharmacology, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-0012, Japan.
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Saika
authors.affiliation: Department of Pharmacology, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-0012, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA.
authors.forename: Mei-Chuan
authors.initials: MC
authors.lastname: Ko
authors.affiliation: Department of Pharmacology, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-0012, Japan. Electronic address: kishioka@wakayama-med.ac.jp.
authors.forename: Shiroh
authors.initials: S
authors.lastname: Kishioka
mesh_terms: D000700:Analgesics; D000818:Animals; D000893:Anti-Inflammatory Agents; D002478:Cells, Cultured; D054405:Chemokine CCL3 / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D053583:Interleukin-1beta / Q000235:genetics* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D009437:Neuralgia; D018722:Nicotinic Agonists / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000502:physiology; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D020032:Tyrphostins / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; D054405:Chemokine CCL3; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D018722:Nicotinic Agonists; D011725:Pyridines; D011978:Receptors, Nicotinic; D050796:STAT3 Transcription Factor; D020032:Tyrphostins; C494087:Stat3 protein, mouse; C419442:TC 2559; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide
keywords: Chemokine; Cytokine; Nicotine