PMID- 31468083
OWN - NLM
STAT- MEDLINE
DCOM- 20200316
LR  - 20231213
IS  - 1420-908X (Electronic)
IS  - 1023-3830 (Linking)
VI  - 68
IP  - 11
DP  - 2019 Nov
TI  - Rapamycin attenuates Tc1 and Tc17 cell responses in cigarette smoke-induced 
      emphysema in mice.
PG  - 957-968
LID - 10.1007/s00011-019-01278-0 [doi]
AB  - OBJECTIVE AND DESIGN: Chronic exposure to cigarette smoke promotes airway 
      inflammation and emphysema accompanied by enhanced CD8(+) interferon (IFN)-gamma(+) 
      T(Tc1) and CD8(+) interleukin (IL)-17(+) T(Tc17) cell responses. The mammalian 
      target of rapamycin (mTOR) has been involved in the pathogenesis of emphysema. 
      Inhibiting mTOR by rapamycin has been reported to alleviate emphysema, but the 
      mechanism is not fully understood. We aimed to explore the effect of rapamycin on 
      Tc1 and Tc17 cell responses induced by cigarette smoke exposure. MATERIALS: Male 
      C57BL/6 mice were exposed to cigarette smoke or room air for 24 weeks. Half of 
      the smoke-exposed mice received rapamycin in the last 12 weeks. The severity of 
      emphysema in those mice was evaluated by mean linear intercept (MLI), mean 
      alveolar airspace area (MAA) and destructive index (DI). Bronchoalveolar lavage 
      was collected and analyzed. Phosphorylated (p-) mTOR in CD8(+) T cells, Tc1 and 
      Tc17 cells were detected by flow cytometry. The relative expression of p-mTOR in 
      lungs was determined by western blot analysis. IFN-gamma and IL-17A levels were 
      detected by enzyme-linked immunosorbent assays. IFN-gamma, mTOR and RAR-related 
      orphan receptor (ROR)gammat mRNA levels were evaluated by the real-time polymerase 
      chain reaction. RESULTS: Elevated p-mTOR expression in CD8(+) T cells and lung 
      tissue was accompanied by the enhanced Tc1 and Tc17 cell responses in lungs of 
      mice exposed to cigarette smoke. Rapamycin reduced inflammatory cells in BALF and 
      decreased MLI, DI and MAA in lungs. Rapamycin decreased p-mTOR expression, and 
      down-regulation of mTOR and RORgammat mRNA levels along with the attenuation of Tc1 
      and Tc17 cell responses in mice with emphysema. CONCLUSIONS: The mTOR was 
      activated in CD8(+) T cells accompanied by the enhanced Tc1 and Tc17 cell 
      responses in cigarette smoke-related pulmonary inflammation. Rapamycin 
      ameliorated emphysema and attenuated Tc1 and Tc17 cell responses probably caused 
      by inhibiting mTOR in cigarette smoke-exposed mice.
FAU - Zhang, Hui
AU  - Zhang H
AD  - Department of Respiratory and Critical Care Medicine, The First Affiliated 
      Hospital of Guangxi Medical University, 530021, Nanning, China.
FAU - Zhou, Xiu
AU  - Zhou X
AD  - Department of Respiratory and Critical Care Medicine, The First Affiliated 
      Hospital of Guangxi Medical University, 530021, Nanning, China.
FAU - Chen, Xin
AU  - Chen X
AD  - Department of Respiratory and Critical Care Medicine, The First Affiliated 
      Hospital of Guangxi Medical University, 530021, Nanning, China.
FAU - Lin, Yuanzhen
AU  - Lin Y
AD  - Department of Respiratory and Critical Care Medicine, The First Affiliated 
      Hospital of Guangxi Medical University, 530021, Nanning, China.
FAU - Qiu, Shilin
AU  - Qiu S
AD  - Department of Respiratory and Critical Care Medicine, The First Affiliated 
      Hospital of Guangxi Medical University, 530021, Nanning, China.
FAU - Zhao, Yun
AU  - Zhao Y
AD  - Department of Respiratory and Critical Care Medicine, The First Affiliated 
      Hospital of Guangxi Medical University, 530021, Nanning, China.
FAU - Tang, Qiya
AU  - Tang Q
AD  - Department of Respiratory and Critical Care Medicine, The First Affiliated 
      Hospital of Guangxi Medical University, 530021, Nanning, China.
FAU - Liang, Yi
AU  - Liang Y
AD  - Department of Respiratory and Critical Care Medicine, The First Affiliated 
      Hospital of Guangxi Medical University, 530021, Nanning, China.
FAU - Zhong, Xiaoning
AU  - Zhong X
AD  - Department of Respiratory and Critical Care Medicine, The First Affiliated 
      Hospital of Guangxi Medical University, 530021, Nanning, China. 
      xnzhong101@sina.com.
LA  - eng
GR  - 81770041/National Natural Science Foundation of China/
GR  - 81800037/National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20190829
PL  - Switzerland
TA  - Inflamm Res
JT  - Inflammation research : official journal of the European Histamine Research 
      Society ... [et al.]
JID - 9508160
RN  - 0 (Smoke)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Bronchoalveolar Lavage Fluid/cytology/immunology
MH  - CD8-Positive T-Lymphocytes/*drug effects/immunology
MH  - Lung/drug effects/immunology/pathology
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Pulmonary Emphysema/drug therapy/*immunology/metabolism/pathology
MH  - Sirolimus/*pharmacology/therapeutic use
MH  - Smoke
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors/genetics/immunology
MH  - Nicotiana
MH  - Tobacco Products
OTO - NOTNLM
OT  - CD8+IFN-gamma+ T cells
OT  - CD8+IL-17+ T cells
OT  - Chronic obstructive pulmonary disease
OT  - Cigarette smoke
OT  - Emphysema
OT  - Rapamycin
EDAT- 2019/08/31 06:00
MHDA- 2020/03/17 06:00
CRDT- 2019/08/31 06:00
PHST- 2019/01/25 00:00 [received]
PHST- 2019/08/19 00:00 [accepted]
PHST- 2019/08/02 00:00 [revised]
PHST- 2019/08/31 06:00 [pubmed]
PHST- 2020/03/17 06:00 [medline]
PHST- 2019/08/31 06:00 [entrez]
AID - 10.1007/s00011-019-01278-0 [pii]
AID - 10.1007/s00011-019-01278-0 [doi]
PST - ppublish
SO  - Inflamm Res. 2019 Nov;68(11):957-968. doi: 10.1007/s00011-019-01278-0. Epub 2019 
      Aug 29.