PMID- 30659954
OWN - NLM
STAT- MEDLINE
DCOM- 20200618
LR  - 20231213
IS  - 1873-6815 (Electronic)
IS  - 0531-5565 (Linking)
VI  - 118
DP  - 2019 Apr
TI  - Budesonide, Aclidinium and Formoterol in combination limit inflammaging processes 
      in bronchial epithelial cells exposed to cigarette smoke.
PG  - 78-87
LID - S0531-5565(18)30381-4 [pii]
LID - 10.1016/j.exger.2019.01.016 [doi]
AB  - Inflammation and cellular senescence (also called inflammaging) are involved in 
      the pathogenesis of premature lung aging, a key driver of chronic obstructive 
      pulmonary disease (COPD). Downregulation of histone deacetylases and FoxO3 
      expression, activation of the ERK 1/2 pathway and IL-8 increase are hallmarks of 
      lung inflammaging. The effects of Budesonide (BUD), Aclidinium (ACL) and 
      Formoterol (FO) on lung inflammaging are unknown. This study was aimed to assess 
      the effects of BUD, ACL and FO in bronchial epithelial cells exposed to cigarette 
      smoke extract (CSE) by evaluating: a) Expression of TLR4 and survivin and LPS 
      binding by flow cytometry; b) expression of HDAC2, HDAC3, SIRT1 and FoxO3 and 
      activation of the ERK 1/2 pathway by western blot; c) IL-8 mRNA levels and 
      release by Real Time-PCR and ELISA, respectively. Reported results show that CSE 
      increased TLR4 and survivin, LPS binding, ERK 1/2 activation, IL-8 release and 
      mRNA levels but decreased SIRT1, HDAC2, HDAC3 and FoxO3 nuclear expression. 
      Combined therapy with BUD, ACL and FO counteracted the effects of CSE on LPS 
      binding, FoxO3 nuclear expression, ERK 1/2 activation, survivin and IL-8 release 
      and mRNA levels. These findings suggest a new role of combination therapy with 
      BUD, ACL and FO in counteracting inflammaging processes induced by cigarette 
      smoke exposure.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
FAU - Ferraro, M
AU  - Ferraro M
AD  - Istituto di Biomedicina e Immunologia Molecolare, Consiglio Nazionale delle 
      Ricerche, Palermo, Italy.
FAU - Di Vincenzo, S
AU  - Di Vincenzo S
AD  - Istituto di Biomedicina e Immunologia Molecolare, Consiglio Nazionale delle 
      Ricerche, Palermo, Italy.
FAU - Dino, P
AU  - Dino P
AD  - Istituto di Biomedicina e Immunologia Molecolare, Consiglio Nazionale delle 
      Ricerche, Palermo, Italy.
FAU - Bucchieri, S
AU  - Bucchieri S
AD  - Istituto di Biomedicina e Immunologia Molecolare, Consiglio Nazionale delle 
      Ricerche, Palermo, Italy.
FAU - Cipollina, C
AU  - Cipollina C
AD  - Istituto di Biomedicina e Immunologia Molecolare, Consiglio Nazionale delle 
      Ricerche, Palermo, Italy; Fondazione Ri.MED, Palermo, Italy.
FAU - Gjomarkaj, M
AU  - Gjomarkaj M
AD  - Istituto di Biomedicina e Immunologia Molecolare, Consiglio Nazionale delle 
      Ricerche, Palermo, Italy.
FAU - Pace, E
AU  - Pace E
AD  - Istituto di Biomedicina e Immunologia Molecolare, Consiglio Nazionale delle 
      Ricerche, Palermo, Italy. Electronic address: pace@ibim.cnr.it.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190116
PL  - England
TA  - Exp Gerontol
JT  - Experimental gerontology
JID - 0047061
RN  - 0 (FOXO3 protein, human)
RN  - 0 (Forkhead Box Protein O3)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Smoke)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Tropanes)
RN  - 51333-22-3 (Budesonide)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 3.5.1.- (SIRT1 protein, human)
RN  - EC 3.5.1.- (Sirtuin 1)
RN  - UQW7UF9N91 (aclidinium bromide)
RN  - W34SHF8J2K (Formoterol Fumarate)
SB  - IM
MH  - Bronchi/*drug effects
MH  - Budesonide/*administration & dosage
MH  - Cells, Cultured
MH  - Cellular Senescence/*drug effects
MH  - Epithelial Cells/*drug effects
MH  - Extracellular Signal-Regulated MAP Kinases/physiology
MH  - Forkhead Box Protein O3/metabolism
MH  - Formoterol Fumarate/*administration & dosage
MH  - Humans
MH  - Inflammation/*prevention & control
MH  - Lipopolysaccharides/metabolism
MH  - Sirtuin 1/analysis
MH  - Smoke/*adverse effects
MH  - Nicotiana/*adverse effects
MH  - Toll-Like Receptor 4/analysis
MH  - Tropanes/*administration & dosage
OTO - NOTNLM
OT  - Bronchial epithelial cells
OT  - Cell senescence
OT  - Cigarette smoke
OT  - Inflammaging
OT  - Inhalatory drugs
EDAT- 2019/01/20 06:00
MHDA- 2020/06/19 06:00
CRDT- 2019/01/20 06:00
PHST- 2018/06/11 00:00 [received]
PHST- 2018/11/21 00:00 [revised]
PHST- 2019/01/14 00:00 [accepted]
PHST- 2019/01/20 06:00 [pubmed]
PHST- 2020/06/19 06:00 [medline]
PHST- 2019/01/20 06:00 [entrez]
AID - S0531-5565(18)30381-4 [pii]
AID - 10.1016/j.exger.2019.01.016 [doi]
PST - ppublish
SO  - Exp Gerontol. 2019 Apr;118:78-87. doi: 10.1016/j.exger.2019.01.016. Epub 2019 Jan 
      16.