PMID- 14530318
OWN - NLM
STAT- MEDLINE
DCOM- 20040106
LR  - 20190516
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 171
IP  - 8
DP  - 2003 Oct 15
TI  - Th1 cytokines regulate adenosine receptors and their downstream signaling 
      elements in human microvascular endothelial cells.
PG  - 3991-8
AB  - We and others have shown that adenosine, acting at its receptors, is a potent 
      modulator of inflammation and angiogenesis. To better understand the regulation 
      of adenosine receptors during these processes we studied the effects of IL-1, 
      TNF-alpha, and IFN-gamma on expression and function of adenosine receptors and 
      select members of their coupling G proteins in human dermal microvascular 
      endothelial cells (HMVEC). HMVEC expressed message and protein for A(2A) and 
      A(2B), but not A(1) or A(3) receptors. IL-1 and TNF-alpha treatment increased 
      message and protein expression of A(2A) and A(2B) receptor. IFN-gamma treatment 
      also increased the expression of A(2B) receptors, but decreased expression of 
      A(2A) receptors. Resting HMVEC and IFN-gamma-treated cells showed minimal cAMP 
      response to the selective A(2A) receptor agonist 
      2-[2-(4-chlorophenyl)ethoxy]adenosine (MRE0094). In contrast, MRE0094 stimulated 
      a dose-dependent increase in cAMP levels in TNF-alpha-treated cells that was 
      almost completely blocked by the A(2A) receptor antagonist ZM-241385 
      (4-[2-[7-amino-2-(2-furyl)[1,2,4]triazolo-[2,3-a][1,3,5]triazin-5-ylamino]ethyl]phenol). 
      The nonselective adenosine receptor agonist 5'-(N-ethylcarboxamido)adenosine 
      increased cAMP levels in both TNF-alpha- and IFN-gamma-treated cells, but not 
      control cells, and its effect was only partially reversed by ZM-241385 in 
      TNF-alpha-treated cells and not affected in IFN-gamma-treated cells. HMVEC 
      expressed a higher level of G protein beta1 isoform than beta4 isoform. Although 
      none of the cytokines tested affected G(beta1) expression, both IL-1 and 
      TNF-alpha significantly up-regulated G(beta4) expression. These findings indicate 
      that inflammatory cytokines modulate adenosine receptor expression and function 
      on HMVECs and suggest that the interaction between proinflammatory cytokines and 
      adenosine receptors may affect therapeutic responses to anti-inflammatory drugs 
      that act via adenosine-dependent mechanisms.
FAU - Nguyen, D Khoa
AU  - Nguyen DK
AD  - Division of Clinical Pharmacology, Department of Medicine, New York University 
      School of Medicine, New York, NY 10016, USA.
FAU - Montesinos, M Carmen
AU  - Montesinos MC
FAU - Williams, Adrienne J
AU  - Williams AJ
FAU - Kelly, Maureen
AU  - Kelly M
FAU - Cronstein, Bruce N
AU  - Cronstein BN
LA  - eng
GR  - AR41911/AR/NIAMS NIH HHS/United States
GR  - CA160877/CA/NCI NIH HHS/United States
GR  - GM56268/GM/NIGMS NIH HHS/United States
GR  - M01RR00096/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Cytokines)
RN  - 0 (GTP-Binding Protein beta Subunits)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Interleukin-1)
RN  - 0 (Phenethylamines)
RN  - 0 (Protein Isoforms)
RN  - 0 (Protein Subunits)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptor, Adenosine A2A)
RN  - 0 (Receptor, Adenosine A2B)
RN  - 0 (Receptors, Purinergic P1)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 120225-54-9 (2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine)
RN  - 82115-62-6 (Interferon-gamma)
RN  - K72T3FS567 (Adenosine)
SB  - IM
MH  - 3' Flanking Region/physiology
MH  - Adenosine/*analogs & derivatives/pharmacology
MH  - Cell Line
MH  - Cytokines/pharmacology/*physiology
MH  - Endothelium, Vascular/cytology/*immunology/*metabolism
MH  - GTP-Binding Protein beta Subunits/biosynthesis
MH  - Humans
MH  - Inflammation Mediators/pharmacology
MH  - Interferon-gamma/pharmacology
MH  - Interleukin-1/pharmacology
MH  - Microcirculation/cytology/immunology/metabolism
MH  - Phenethylamines/pharmacology
MH  - Protein Isoforms/biosynthesis
MH  - Protein Subunits/biosynthesis
MH  - RNA, Messenger/biosynthesis
MH  - Receptor, Adenosine A2A/biosynthesis/metabolism
MH  - Receptor, Adenosine A2B/biosynthesis/metabolism
MH  - Receptors, Purinergic P1/biosynthesis/*metabolism/physiology
MH  - Signal Transduction/*immunology
MH  - Th1 Cells/*immunology/*metabolism
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - Up-Regulation/immunology
MH  - Vascular Endothelial Growth Factor A/biosynthesis/genetics
EDAT- 2003/10/08 05:00
MHDA- 2004/01/07 05:00
CRDT- 2003/10/08 05:00
PHST- 2003/10/08 05:00 [pubmed]
PHST- 2004/01/07 05:00 [medline]
PHST- 2003/10/08 05:00 [entrez]
AID - 10.4049/jimmunol.171.8.3991 [doi]
PST - ppublish
SO  - J Immunol. 2003 Oct 15;171(8):3991-8. doi: 10.4049/jimmunol.171.8.3991.