PMID- 28483577
OWN - NLM
STAT- MEDLINE
DCOM- 20181126
LR  - 20181126
IS  - 0925-4439 (Print)
IS  - 0925-4439 (Linking)
VI  - 1863
IP  - 7
DP  - 2017 Jul
TI  - Formoterol and fluticasone propionate combination improves histone deacetylation 
      and anti-inflammatory activities in bronchial epithelial cells exposed to 
      cigarette smoke.
PG  - 1718-1727
LID - S0925-4439(17)30140-0 [pii]
LID - 10.1016/j.bbadis.2017.05.003 [doi]
AB  - BACKGROUND: The addition of long-acting beta2-agonists (LABAs) to corticosteroids 
      improves asthma control. Cigarette smoke exposure, increasing oxidative stress, 
      may negatively affect corticosteroid responses. The anti-inflammatory effects of 
      formoterol (FO) and fluticasone propionate (FP) in human bronchial epithelial 
      cells exposed to cigarette smoke extracts (CSE) are unknown. AIMS: This study 
      explored whether FP, alone and in combination with FO, in human bronchial 
      epithelial cellline (16-HBE) and primary bronchial epithelial cells (NHBE), 
      counteracted some CSE-mediated effects and in particular some of the molecular 
      mechanisms of corticosteroid resistance. METHODS: 16-HBE and NHBE were stimulated 
      with CSE, FP and FO alone or combined. HDAC3 and HDAC2 activity, nuclear 
      translocation of GR and NF-kappaB, pERK1/2/tERK1/2 ratio, IL-8, TNF-alpha, IL-1beta mRNA 
      expression, and mitochondrial ROS were evaluated. Actin reorganization in 
      neutrophils was assessed by fluorescence microscopy using the phalloidin method. 
      RESULTS: In 16-HBE, CSE decreased expression/activity of HDAC3, activity of 
      HDAC2, nuclear translocation of GR and increased nuclear NF-kappaB expression, pERK 
      1/2/tERK1/2 ratio, and mRNA expression of inflammatory cytokines. In NHBE, CSE 
      increased mRNA expression of inflammatory cytokines and supernatants from CSE 
      exposed NHBE increased actin reorganization in neutrophils. FP combined with FO 
      reverted all these phenomena in CSE stimulated 16-HBE cells as well as in NHBE 
      cells. CONCLUSIONS: The present study provides compelling evidences that FP 
      combined with FO may contribute to revert some processes related to steroid 
      resistance induced by oxidative stress due to cigarette smoke exposure increasing 
      the anti-inflammatory effects of FP.
CI  - Copyright (c) 2017 Elsevier B.V. All rights reserved.
FAU - Ferraro, M
AU  - Ferraro M
AD  - Istituto di Biomedicina e Immunologia Molecolare, Consiglio Nazionale delle 
      Ricerche, Palermo, Italy. Electronic address: ferraro@ibim.cnr.it.
FAU - Gjomarkaj, M
AU  - Gjomarkaj M
AD  - Istituto di Biomedicina e Immunologia Molecolare, Consiglio Nazionale delle 
      Ricerche, Palermo, Italy.
FAU - Siena, L
AU  - Siena L
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 - Pace, E
AU  - Pace E
AD  - Istituto di Biomedicina e Immunologia Molecolare, Consiglio Nazionale delle 
      Ricerche, Palermo, Italy.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170505
PL  - Netherlands
TA  - Biochim Biophys Acta Mol Basis Dis
JT  - Biochimica et biophysica acta. Molecular basis of disease
JID - 101731730
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Histones)
RN  - CUT2W21N7U (Fluticasone)
RN  - W34SHF8J2K (Formoterol Fumarate)
SB  - IM
MH  - Acetylation/drug effects
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Bronchi/*metabolism/pathology
MH  - Cigarette Smoking/*adverse effects
MH  - Epithelial Cells/*metabolism/pathology
MH  - Fluticasone/*pharmacology
MH  - Formoterol Fumarate/*pharmacology
MH  - Gene Expression Regulation/drug effects
MH  - Histones/*metabolism
MH  - Humans
OTO - NOTNLM
OT  - Bronchial epithelial cells
OT  - Cigarette smoke
OT  - Corticosteroids
OT  - Long-acting beta2-agonists
EDAT- 2017/05/10 06:00
MHDA- 2018/11/27 06:00
CRDT- 2017/05/10 06:00
PHST- 2017/01/11 00:00 [received]
PHST- 2017/04/20 00:00 [revised]
PHST- 2017/05/04 00:00 [accepted]
PHST- 2017/05/10 06:00 [pubmed]
PHST- 2018/11/27 06:00 [medline]
PHST- 2017/05/10 06:00 [entrez]
AID - S0925-4439(17)30140-0 [pii]
AID - 10.1016/j.bbadis.2017.05.003 [doi]
PST - ppublish
SO  - Biochim Biophys Acta Mol Basis Dis. 2017 Jul;1863(7):1718-1727. doi: 
      10.1016/j.bbadis.2017.05.003. Epub 2017 May 5.