التفاصيل البيبلوغرافية
| العنوان: |
Studying α7 nicotinic receptor anti‐inflammatory signaling |
| المؤلفون: |
Loring, Ralph, Garg, Brijesh |
| المصدر: |
The FASEB Journal ; volume 29, issue S1 ; ISSN 0892-6638 1530-6860 |
| بيانات النشر: |
Wiley |
| سنة النشر: |
2015 |
| المجموعة: |
Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: |
α7 nicotinic receptors (α7 AChRs) reportedly play anti‐inflammatory roles in innate immune function, in part by blocking the transcription factor NFkB. We tested whether heterologously expressed α7 AChRs directly interact with NFkB signaling in the rat pituitary cell line GH3. GH3 cells show significant 125 I‐α‐bungarotoxin (BT) binding when transfected with rat α7 nAChR, but in our hands, commercially available α7 antibodies do not detect α7 AChR in these transfected cells. For instance, α7 AChR‐GFP chimeras transfected into cells show BT binding, and anti‐GFP staining, but not anti‐α7 AChR staining in Western blots. Upon transfection with an NFkB promoter driving secreted alkaline phosphatase (NFkB‐SEAP), GH3 cells show up to 30 fold increases in SEAP secretion following 1‐100 ng/ml rat tumor necrosis factor (TNF) treatment. Nicotine (100 ‐1000 μM) and the selective α7 AChR agonist PNU282987 (PNU, 50‐300 μM) blocked TNF‐stimulated SEAP secretion in GH3 cells transfected with NFkB‐SEAP alone, while GTS21 did not. This suggests some nicotinic compounds have direct effects on NFkB signaling in non‐immune cells, since transfection with α7 had no further effect. To understand whether reported α7 AChR anti‐inflammatory effects are cell‐type dependent, we investigated α7 AChR drug effects in macrophage‐like cells (RAW 264.7 cells) using PNU, GTS21 and nicotine following lipopolysaccharide (LPS) stimulation (10 ng/ml). GTS21 (50‐200 µM) blocked LPS‐induced TNF release from RAW cells, but nicotine and PNU did not. Our findings suggest that α7 AChR do not directly interact with and subsequently block NFKB signaling, and that additional factors are required in heterologous cells to mimic the reported α7 AChR‐mediated anti‐inflammatory effects in immune cells. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.1096/fasebj.29.1_supplement.lb510 |
| الاتاحة: |
http://dx.doi.org/10.1096/fasebj.29.1_supplement.lb510 |
| Rights: |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
| رقم الانضمام: |
edsbas.81CE781D |
| قاعدة البيانات: |
BASE |