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Middle cerebral artery occlusion reduces α7 nicotinic receptor expression whereas α7 nicotinic receptor stimulation suppresses inflammation and promotes microglial Mox phenotype (877.7)
Author(s) -
Hua Sansan,
Darsalia Vladimer,
Patrone Cesare,
Mallard Carina,
Johansson Maria
Publication year - 2014
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.28.1_supplement.877.7
Subject(s) - microglia , agonist , stimulation , inflammation , receptor , medicine , pharmacology , immunology , chemistry , endocrinology
Inflammation plays a central role in ischemic stroke. During brain inflammation the resident macrophages of the brain, the microglia cells, are rapidly activated. In the periphery, α7 nicotinic acetylcholine receptors (α7R) present on macrophages can regulate inflammation by suppressing cytokine release. In the current study we investigated the expression α7R in mice after middle cerebral artery occlusion (MCAO). We further examined possible anti‐inflammatory role of α7R stimulation in vitro and microglia polarization after α7R agonist treatment. Real‐time PCR analysis showed a 58% reduction in α7R expression 72 h post MCAO. Stimulation of primary microglial cells with LPS in combination with increasing doses of the selective α7R agonist AR‐R 17779 significantly attenuated TNF‐α release and increased α7R transcript in microglial cells. Gene expression of M1 markers CD86 and iNOS, as well as M2 markers CD206 and Arginase1 was not influenced by LPS and/or α7R agonist treatment, however, Mox markers heme oxygenase (Hmox1) and sulforedoxin‐1 (Srx1) were significantly increased, suggesting a polarization towards the Mox phenotype after α7R stimulation. Thus, our data support the anti‐inflammatory role of α7R in the brain after MCAO and in microglia, suggesting that α7R stimulation could enhance the polarization towards a reparative Mox phenotype.