| Project/Area Number |
15K09544
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Collagenous pathology/Allergology
|
|---|
| Research Institution | National Hospital Organization Osaka-Minami Medical Center |
|---|
Principal Investigator |
Saeki Yukihiko 独立行政法人国立病院機構(大阪南医療センター臨床研究部), その他部局等, 臨床研究部長 (40240840)
|
|---|
| Project Period (FY) |
2015-04-01 – 2018-03-31
|
| Project Status |
Completed (Fiscal Year 2017)
|
| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
|---|
| Keywords | 関節リウマチ / ＴＮＦ阻害薬 / 喫煙 / NF-ｋB / ＡｈＲ / クロストーク / TNF阻害薬 / AhR / NF-kB / 生物学的製剤 / TNF |
|---|
| Outline of Final Research Achievements |
To investigate the influence of smoking on biologics treatment in RA, the association between discontinuation due to poor therapeutic response and smoking status was analyzed in a cross-sectional way by using the“NinJa” Registry of Japanese patients with RA, by a multivariable logistic regression analysis. The rate of discontinuation due to poor therapeutic response was significantly higher in the patients with current smoking compared to those with either never- or ever-smoking in the TNF-inhibitor (TNF-i)treatment group. Using an immortalized rheumatoid synovial cell line, MH7A, cigarette chemical compounds known as AhRligands, themselves activated NF-kB and induced proinflammatory cytokines.They enhanced both TNFa-induced NF-kB activation and proinflammatory cytokine production. This enhancement was diminished significantly by a NF-kB inhibitor, suggesting a crosstalk between TNFa and smoke signalings in NF-kB activation.This may cause treatment failure of TNF-iin RA.
|
