PMID- 20085598
OWN - NLM
STAT- MEDLINE
DCOM- 20100416
LR  - 20171116
IS  - 1365-2222 (Electronic)
IS  - 0954-7894 (Linking)
VI  - 39
IP  - 12
DP  - 2009 Dec
TI  - Theophylline inhibits the differentiation of human monocyte into dendritic cell 
      potentially via adenosine receptor antagonism.
PG  - 1857-65
LID - 10.1111/j.1365-2222.2009.03365.x [doi]
AB  - BACKGROUND: Theophylline has an anti-inflammatory action that may account for its 
      clinical effectiveness in the reduction of inflammatory cells in the airways. 
      Dendritic cells (DCs) are professional antigen-presenting cells, capable of 
      priming naive T cells, and play key roles in the activation of immune responses 
      in asthma. OBJECTIVE: The purpose of this study was to investigate the effects of 
      theophylline on human monocyte differentiation into DCs and whether this involved 
      antagonism of adenosine receptors. METHODS: Peripheral human blood monocytes were 
      cultured in the presence of granulocyte/macrophage-colony stimulating factor and 
      IL-4 to induce DC differentiation. The cells were incubated with theophylline, 
      KF17837 (a selective A2a receptor antagonist) and enprofylline (A2b receptor 
      antagonist) and co-incubated with selective adenosine A1 and A2a receptor 
      agonists, a phosphodiesterase inhibitor (rolipram) and adenosine deaminase (ADA) 
      to determine their effects on DC differentiation. In addition, depletion of 
      adenosine receptors by small interfering RNA (siRNA) was also examined. RESULTS: 
      Monocytes differentiated into myeloid DCs in the culture system. The number of 
      DCs was remarkably reduced by 60-70% when theophylline was administered at a 
      therapeutic concentration. This effect was concentration-dependently exacerbated, 
      was partly mediated by cellular apoptosis and was effectively reversed by the 
      addition of the A1 agonists [2-chloro-N(6)-cyclopentyladenosin, 
      N(6)-cyclohexyladenosine, and N-ethylcarboxamidoadenosine (NECA)] or the A2a 
      agonist (CGS-21680, NECA). The depletion of the adenosine A1 receptor by siRNA 
      and addition of ADA remarkably reduced DC differentiation. Meanwhile, both 
      enprofylline and rolipram had little effect. CONCLUSION: Our findings suggest 
      that the adenosine A1 (and possibly coordinated with A2a) receptors contribute to 
      DC differentiation and survival. These findings provide further evidence that 
      theophylline has an anti-inflammatory action in bronchial asthma.
FAU - Yasui, K
AU  - Yasui K
AD  - Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama 
      University Graduate School of Medicine, Okayama, Japan. 
      k-yasui@md.okayama-u.ac.jp
FAU - Kondo, Y
AU  - Kondo Y
FAU - Wada, T
AU  - Wada T
FAU - Yashiro, M
AU  - Yashiro M
FAU - Tsuge, M
AU  - Tsuge M
FAU - Morishima, T
AU  - Morishima T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Clin Exp Allergy
JT  - Clinical and experimental allergy : journal of the British Society for Allergy 
      and Clinical Immunology
JID - 8906443
RN  - 0 (Adenosine A1 Receptor Agonists)
RN  - 0 (Adenosine A2 Receptor Agonists)
RN  - 0 (Adenosine A2 Receptor Antagonists)
RN  - 0 (CD11c Antigen)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (IL4 protein, human)
RN  - 0 (Phenethylamines)
RN  - 0 (Purinergic P1 Receptor Agonists)
RN  - 0 (Purinergic P1 Receptor Antagonists)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptor, Adenosine A1)
RN  - 0 (Receptors, Purinergic P1)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Xanthines)
RN  - 120225-54-9 (2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine)
RN  - 152881-18-0 (KF 17837)
RN  - 207137-56-2 (Interleukin-4)
RN  - 35920-39-9 (Adenosine-5'-(N-ethylcarboxamide))
RN  - 36396-99-3 (N(6)-cyclohexyladenosine)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
RN  - C137DTR5RG (Theophylline)
RN  - DT7DT5E518 (enprofylline)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.5.4.4 (Adenosine Deaminase)
RN  - K676NL63N7 (Rolipram)
RN  - K72T3FS567 (Adenosine)
SB  - IM
MH  - Adenosine/analogs & derivatives/pharmacology
MH  - Adenosine A1 Receptor Agonists
MH  - Adenosine A2 Receptor Agonists
MH  - Adenosine A2 Receptor Antagonists
MH  - Adenosine Deaminase/pharmacology
MH  - Adenosine-5'-(N-ethylcarboxamide)/pharmacology
MH  - Adult
MH  - Apoptosis/drug effects
MH  - CD11c Antigen/metabolism
MH  - Caspase 3/metabolism
MH  - Cell Differentiation/*drug effects
MH  - Dendritic Cells/*cytology/metabolism
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology
MH  - HLA-DR Antigens/metabolism
MH  - Humans
MH  - Interleukin-4/pharmacology
MH  - Male
MH  - Monocytes/*cytology/drug effects
MH  - Phenethylamines/pharmacology
MH  - Purinergic P1 Receptor Agonists
MH  - *Purinergic P1 Receptor Antagonists
MH  - RNA, Small Interfering/genetics
MH  - Receptor, Adenosine A1/genetics
MH  - Receptors, Purinergic P1/physiology
MH  - Recombinant Proteins
MH  - Rolipram/pharmacology
MH  - Theophylline/*pharmacology
MH  - Xanthines/pharmacology
EDAT- 2010/01/21 06:00
MHDA- 2010/04/17 06:00
CRDT- 2010/01/21 06:00
PHST- 2010/01/21 06:00 [entrez]
PHST- 2010/01/21 06:00 [pubmed]
PHST- 2010/04/17 06:00 [medline]
AID - CEA3365 [pii]
AID - 10.1111/j.1365-2222.2009.03365.x [doi]
PST - ppublish
SO  - Clin Exp Allergy. 2009 Dec;39(12):1857-65. doi: 10.1111/j.1365-2222.2009.03365.x.