PMID- 26498483
OWN - NLM
STAT- MEDLINE
DCOM- 20160711
LR  - 20220318
IS  - 1465-993X (Electronic)
IS  - 1465-9921 (Print)
IS  - 1465-9921 (Linking)
VI  - 16
DP  - 2015 Oct 24
TI  - Cigarette smoke differentially modulates dendritic cell maturation and function 
      in time.
PG  - 131
LID - 10.1186/s12931-015-0291-6 [doi]
LID - 131
AB  - BACKGROUND: Dendritic cells (DCs) as professional antigen presenting cells (APCs) 
      play a critical role in the regulation of host immune responses. DCs evolve from 
      immature, antigen-capturing cells, to mature antigen-presenting cells. The 
      relative contribution of DCs to cigarette smoke-induced inflammation is not well 
      documented. In the current study, we investigated a modulatory effect of 
      cigarette smoke extract (CSE) on differentiation, maturation and function of DCs. 
      METHODS: Primary murine DCs were grown from bone marrow cells with GM-CSF. 
      Development of DC was analyzed by expression of CD11c, MHCII, CD86, CD40 and CD83 
      using flow cytometry. Murine DC's and human L428 cells were co-cultured with CSE 
      for various periods of time. Functional activity was analyzed by measuring 
      FITC-dextran uptake, cytokine production and the ability to stimulate T cell 
      activation in a mixed lymphocyte reaction. RESULTS: Our results show that 
      short-term CSE stimulation (~24 h) influence the maturation status of newly 
      differentiated and immature DCs towards more mature cells as revealed by 
      upregulation of MHCII, CD83, CD86, CD40, reduction in antigen up-take capacity 
      and enhanced secretion of pro-inflammatory (IL-12, IL-6 and TNF-alpha) cytokines. 
      Interestingly, long-term CSE exposure, time- and concentration-dependently, 
      suppressed the development of functional DCs. This suppression was demonstrated 
      by a decline in CD11c/MHCII, CD83, CD86 and CD40 expression, the production of 
      cytokines and ability to stimulate T lymphocytes. Moreover, CSE significantly 
      suppressed the endocytosis function of mouse DCs which was not due to diminished 
      DC viability. Similar to mouse DCs, long-term co-culturing of the human L428 DC 
      cell line with CSE time-dependently suppressed the expression of CD54. 
      CONCLUSIONS: The present study provides evidence that CSE modulates DC-mediated 
      immune responses via affecting both the function and maturation of DCs. The 
      suppressive effects of cigarette smoke on DC function might lead to impaired 
      immune responses to various infections.
FAU - Givi, Masoumeh Ezzati
AU  - Givi ME
AD  - Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty 
      of Science, Utrecht University, PO BOX 80082, 3508, TB, Utrecht, The Netherlands.
AD  - Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Shahid 
      Chamran University, Ahvaz, Iran.
FAU - Folkerts, Gert
AU  - Folkerts G
AD  - Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty 
      of Science, Utrecht University, PO BOX 80082, 3508, TB, Utrecht, The Netherlands.
FAU - Wagenaar, Gerry T M
AU  - Wagenaar GT
AD  - Department of Pediatrics, Division of Neonatology, Leiden University Medical 
      Center, Leiden, The Netherlands.
FAU - Redegeld, Frank A
AU  - Redegeld FA
AD  - Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty 
      of Science, Utrecht University, PO BOX 80082, 3508, TB, Utrecht, The Netherlands. 
      f.a.m.redegeld@uu.nl.
FAU - Mortaz, Esmaeil
AU  - Mortaz E
AD  - Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty 
      of Science, Utrecht University, PO BOX 80082, 3508, TB, Utrecht, The Netherlands.
AD  - Chronic Respiratory Diseases Research Center and National Research Institute of 
      Tuberculosis and Lung Diseases (NRITLD), Department of Immunology, Shahid 
      Beheshti University of Medical Sciences, Tehran, Iran.
AD  - Airways Disease Section, National Heart and Lung Institute, Imperial College 
      London, London, UK.
LA  - eng
PT  - Journal Article
DEP - 20151024
PL  - England
TA  - Respir Res
JT  - Respiratory research
JID - 101090633
RN  - 0 (Biomarkers)
RN  - 0 (Cytokines)
RN  - 0 (Smoke)
SB  - IM
MH  - Biomarkers/metabolism
MH  - Cell Differentiation/*drug effects
MH  - Cell Line, Tumor
MH  - Coculture Techniques
MH  - Cytokines/metabolism
MH  - Dendritic Cells/*drug effects/immunology/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Humans
MH  - Lymphocyte Activation/*drug effects
MH  - Phenotype
MH  - Smoke/*adverse effects
MH  - Smoking/*adverse effects
MH  - T-Lymphocytes/immunology/metabolism
MH  - Time Factors
PMC - PMC4619524
EDAT- 2015/10/27 06:00
MHDA- 2016/07/12 06:00
PMCR- 2015/10/24
CRDT- 2015/10/27 06:00
PHST- 2014/12/16 00:00 [received]
PHST- 2015/10/13 00:00 [accepted]
PHST- 2015/10/27 06:00 [entrez]
PHST- 2015/10/27 06:00 [pubmed]
PHST- 2016/07/12 06:00 [medline]
PHST- 2015/10/24 00:00 [pmc-release]
AID - 10.1186/s12931-015-0291-6 [pii]
AID - 291 [pii]
AID - 10.1186/s12931-015-0291-6 [doi]
PST - epublish
SO  - Respir Res. 2015 Oct 24;16:131. doi: 10.1186/s12931-015-0291-6.