PMID- 9743553
OWN - NLM
STAT- MEDLINE
DCOM- 19981016
LR  - 20131121
IS  - 0008-8749 (Print)
IS  - 0008-8749 (Linking)
VI  - 188
IP  - 1
DP  - 1998 Aug 25
TI  - A carbocyclic nucleoside analogue is a TNF-alpha inhibitor with immunosuppressive 
      action: role of prostaglandin E2 and protein kinase C and comparison with 
      pentoxifylline.
PG  - 12-8
AB  - Tumor necrosis factor-alpha (TNF-alpha) is associated with several acute and 
      chronic inflammatory conditions. New therapies directed at inhibiting TNF-alpha 
      will be important in treating pathological processes mediated by TNF-alpha. In 
      this study, we studied and compared the effect of the carbocyclic nucleoside 
      analogue (9-[(1R, 3R)-trans-cyclopentan-3-ol] adenine) with pentoxifylline on 
      modulating TNF-alpha production. The carbocyclic nucleoside analogue inhibited 
      TNF-alpha production in a dose-dependent manner (1 microM-1 mM) by stimulated 
      peripheral blood mononuclear cells and cell lines of both monocyte (THP-1) and 
      T-lymphocyte phenotypes (CEM x 174). The drug potently inhibited TNF production 
      in cells stimulated by endotoxin, the superantigen (staphylococci enterotoxin A), 
      the mitogen (phytohemagglutinin), and the protein kinase C activator (phorbol 
      myristate acetate) with ED50 ranging from 5 to 30 microM. At moderate 
      concentrations, the carbocyclic nucleoside analogue inhibited superantigen (ED50 
      = 300 microM) and alloantigen (mixed lymphocyte reaction) T cell proliferative 
      responses (ED50 = 150 microM). The involvement of protein kinase C and 
      prostaglandin E2 (PGE2), mediators that regulate TNF-alpha production, was also 
      investigated. Unlike PTX, the nucleoside analogue did not upregulate PGE2 
      production. The inhibition of TNF-alpha production appeared to be mediated at 
      least partly by PKC, since the nucleoside analogue caused suppression of PKC 
      activity in stimulated cells. The results show that the carbocyclic nucleoside 
      analogue is a TNF-alpha inhibitor that may be appropriate in the therapy of 
      TNF-alpha-associated complications. The suppressive properties of the carbocyclic 
      nucleoside analogue on antigen and alloantigen (mixed lymphocyte reaction) 
      responses may be appropriate in disease conditions in which inhibiting both 
      TNF-alpha and T-cell reactivity is desirable.
CI  - Copyright 1998 Academic Press.
FAU - Al-Humidan, A
AU  - Al-Humidan A
AD  - Interferon and Cytokine Research, King Faisal Specialist Hospital and Research 
      Center, Riyadh, 11211, Saudi Arabia.
FAU - Edwards, C K
AU  - Edwards CK
FAU - Al-Sofi, A
AU  - Al-Sofi A
FAU - Dzimiri, M
AU  - Dzimiri M
FAU - Al-Sedairy, S T
AU  - Al-Sedairy ST
FAU - Khabar, K S
AU  - Khabar KS
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - Netherlands
TA  - Cell Immunol
JT  - Cellular immunology
JID - 1246405
RN  - 0 (3-(6-amino-9H-purin-9-yl)-cyclopentanol)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Interleukin-8)
RN  - 0 (Isoantigens)
RN  - 0 (Phosphodiesterase Inhibitors)
RN  - 0 (Superantigens)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - JAC85A2161 (Adenine)
RN  - K7Q1JQR04M (Dinoprostone)
RN  - SD6QCT3TSU (Pentoxifylline)
SB  - IM
MH  - Adenine/*analogs & derivatives/pharmacology/toxicity
MH  - Dinoprostone/physiology
MH  - Humans
MH  - Immunosuppressive Agents/*pharmacology
MH  - Interleukin-8/metabolism
MH  - Isoantigens/pharmacology
MH  - Leukocytes, Mononuclear/drug effects
MH  - Lymphocyte Culture Test, Mixed
MH  - Pentoxifylline/pharmacology
MH  - Phosphodiesterase Inhibitors/pharmacology
MH  - Protein Kinase C/physiology
MH  - Superantigens/pharmacology
MH  - T-Lymphocytes/chemistry/immunology/metabolism
MH  - Tumor Necrosis Factor-alpha/*antagonists & inhibitors/metabolism
EDAT- 1998/09/23 00:00
MHDA- 1998/09/23 00:01
CRDT- 1998/09/23 00:00
PHST- 1998/09/23 00:00 [pubmed]
PHST- 1998/09/23 00:01 [medline]
PHST- 1998/09/23 00:00 [entrez]
AID - S0008-8749(98)91324-7 [pii]
AID - 10.1006/cimm.1998.1324 [doi]
PST - ppublish
SO  - Cell Immunol. 1998 Aug 25;188(1):12-8. doi: 10.1006/cimm.1998.1324.