PMID- 27262379
OWN - NLM
STAT- MEDLINE
DCOM- 20170310
LR  - 20170827
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 786
DP  - 2016 Sep 5
TI  - Adalimumab ameliorates OVA-induced airway inflammation in mice: Role of CD4(+) 
      CD25(+) FOXP3(+) regulatory T-cells.
PG  - 100-108
LID - S0014-2999(16)30360-0 [pii]
LID - 10.1016/j.ejphar.2016.06.002 [doi]
AB  - Asthma is a chronic inflammatory heterogeneous disorder initiated by a 
      dysregulated immune response which drives disease development in susceptible 
      individuals. Though T helper 2 (TH2) biased responses are usually linked to 
      eosinophilic asthma, other Th cell subsets induce neutrophilic airway 
      inflammation which provokes the most severe asthmatic phenotypes. A growing 
      evidence highlights the role of T regulatory (Treg) cells in damping abnormal Th 
      responses and thus inhibiting allergy and asthma. Therefore, strategies to induce 
      or augment Treg cells hold promise for treatment and prevention of allergic 
      airway inflammation. Recently, the link between Tumor necrosis factor-alpha (TNF-alpha) 
      and Treg has been uncovered, and TNF-alpha antagonists are increasingly used in many 
      autoimmune diseases. Yet, their benefits in allergic airway inflammation is not 
      clarified. We investigated the effect of Adalimumab, a TNF-alpha antagonist, on 
      Ovalbumin (OVA)-induced allergic airway inflammation in CD1 mice and explored its 
      impact on Treg cells. Our results showed that Adalimumab treatment attenuated the 
      OVA-induced increase in serum IgE, TH2 and TH1 derived inflammatory cytokines 
      (IL-4 and IFN-gamma, respectively) in bronchoalveolar lavage (BAL) fluid, suppressed 
      recruitment of inflammatory cells in BAL fluid and lung, and inhibited BAL fluid 
      neutrophilia. It also ameliorated goblet cell metaplasia and bronchial fibrosis. 
      Splenocytes flow cytometry revealed increased percentage of CD4(+) CD25(+) 
      FOXP3(+) Treg cells by Adalimumab that was associated with increase in their 
      suppressive activity as shown by elevated BAL fluid IL-10. We conclude that the 
      beneficial effects of Adalimumab in this CD1 neutrophilic model of allergic 
      airway inflammation are attributed to augmentation of Treg cell number and 
      activity.
CI  - Copyright (c) 2016 Elsevier B.V. All rights reserved.
FAU - Elsakkar, Mohamed G
AU  - Elsakkar MG
AD  - Department of Clinical Pharmacology, Faculty of Medicine, Alexandria University, 
      Alexandria, Egypt.
FAU - Sharaki, Olla A
AU  - Sharaki OA
AD  - Department of Clinical and Chemical Pathology, Faculty of Medicine, Alexandria 
      University, Alexandria, Egypt.
FAU - Abdallah, Dina M
AU  - Abdallah DM
AD  - Department of Pathology, Faculty of Medicine, Alexandria University, Alexandria, 
      Egypt.
FAU - Mostafa, Dalia K
AU  - Mostafa DK
AD  - Department of Clinical Pharmacology, Faculty of Medicine, Alexandria University, 
      Alexandria, Egypt. Electronic address: dalia.kashishy@alexmed.edu.eg.
FAU - Shekondali, Fadia T
AU  - Shekondali FT
AD  - Department of Pharmacology, Faculty of Medicine, EL-Zawia University, Libya.
LA  - eng
PT  - Journal Article
DEP - 20160602
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Cytokines)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (Foxp3 protein, mouse)
RN  - 0 (Interleukin-2 Receptor alpha Subunit)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 9006-59-1 (Ovalbumin)
RN  - FYS6T7F842 (Adalimumab)
SB  - IM
MH  - Adalimumab/*pharmacology/therapeutic use
MH  - Animals
MH  - Asthma/complications/*drug therapy/immunology/metabolism
MH  - Bronchoalveolar Lavage Fluid
MH  - Cytokines/metabolism
MH  - Forkhead Transcription Factors/*metabolism
MH  - Hyperplasia/complications
MH  - Immunoglobulin E/blood
MH  - Interleukin-2 Receptor alpha Subunit/*metabolism
MH  - Leukocytosis/complications
MH  - Lung/drug effects/immunology/pathology
MH  - Male
MH  - Mice
MH  - Ovalbumin/*immunology
MH  - Pulmonary Fibrosis/complications
MH  - Spleen/immunology
MH  - T-Lymphocytes, Regulatory/*drug effects/immunology/metabolism
OTO - NOTNLM
OT  - Adalimumab
OT  - Adalimumab (PubChem SID: 50070208)
OT  - Airway inflammation
OT  - Aluminum Hydroxide (PubChem CID: 6328211)
OT  - Asthma
OT  - FOXP3(+) Treg cells
OT  - IL-10 (PubChem CID: 146070)
OT  - Neutrophils
OT  - Ovalbumin (PubChem CID: 71311993 )
OT  - Phosphate buffered saline (PubChem CID: 24978514)
OT  - TNF-alpha
EDAT- 2016/06/06 06:00
MHDA- 2017/03/11 06:00
CRDT- 2016/06/06 06:00
PHST- 2016/01/31 00:00 [received]
PHST- 2016/05/23 00:00 [revised]
PHST- 2016/06/01 00:00 [accepted]
PHST- 2016/06/06 06:00 [entrez]
PHST- 2016/06/06 06:00 [pubmed]
PHST- 2017/03/11 06:00 [medline]
AID - S0014-2999(16)30360-0 [pii]
AID - 10.1016/j.ejphar.2016.06.002 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2016 Sep 5;786:100-108. doi: 10.1016/j.ejphar.2016.06.002. Epub 
      2016 Jun 2.