PMID- 14645663
OWN - NLM
STAT- MEDLINE
DCOM- 20040116
LR  - 20031203
IS  - 0026-895X (Print)
IS  - 0026-895X (Linking)
VI  - 64
IP  - 6
DP  - 2003 Dec
TI  - A novel synthetic cannabinoid derivative inhibits inflammatory liver damage via 
      negative cytokine regulation.
PG  - 1334-41
AB  - The therapeutic potential of cannabinoids has been described previously for 
      several inflammatory diseases, but the molecular mechanisms underlying the 
      anti-inflammatory properties of cannabinoids are not well understood. In this 
      study, we investigated the mechanism of action of a novel synthetic cannabinoid, 
      [(+)(6aS,10aS)-6,6-Dimethyl-3-(1,1-dimethylheptyl)-1-hydroxy-9-(1H-imidazol-2-ylsulfanylmethyl]-6a,7,10,10a-tetrahydro-6H-dibenzo[b,d]pyran 
      (PRS-211,092) that has no psychotropic effects but exhibits immunomodulatory 
      properties. Treatment with PRS-211,092 significantly decreased Concanavalin 
      A-induced liver injury in mice that was accompanied by: 1) promotion of early 
      gene expression of interleukin (IL)-6 and IL-10 that play a protective role in 
      this model; 2) induction of early gene expression of the suppressors of cytokine 
      signaling (SOCS-1 and 3), followed by 3) inhibition of several pro-inflammatory 
      mediators, including IL-2, monocyte chemoattractant protein-1 (MCP-1), IL-1beta, 
      interferon-gamma, and tumor necrosis factor alpha. Based on these results, we 
      propose a mechanism by which PRS-211,092 stimulates the expression of IL-6, IL-10 
      and the SOCS proteins that, in turn, negatively regulates the expression of 
      pro-inflammatory cytokines. Negative regulation by PRS-211,092 was further 
      demonstrated in cultured T cells, where it inhibited IL-2 production and nuclear 
      factor of activated T cells activity. These findings suggest that this 
      cannabinoid derivative is an immunomodulator that could be developed as a 
      potential drug for hepatitis as well as for other short- or long-term 
      inflammatory diseases.
FAU - Lavon, Iris
AU  - Lavon I
AD  - Pharmos LTD, Kiryat Weizmann, Bld #13b, Rehovot 76326, Israel. 
      lavoni@netvision.net.il
FAU - Sheinin, Tatiana
AU  - Sheinin T
FAU - Meilin, Sigal
AU  - Meilin S
FAU - Biton, Efrat
AU  - Biton E
FAU - Weksler, Ayelet
AU  - Weksler A
FAU - Efroni, Gilat
AU  - Efroni G
FAU - Bar-Joseph, Avi
AU  - Bar-Joseph A
FAU - Fink, George
AU  - Fink G
FAU - Avraham, Ayelet
AU  - Avraham A
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Mol Pharmacol
JT  - Molecular pharmacology
JID - 0035623
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Cannabinoids)
RN  - 0 (Cytokines)
RN  - 11028-71-0 (Concanavalin A)
SB  - IM
MH  - Adjuvants, Immunologic/chemical synthesis/pharmacology/therapeutic use
MH  - Animals
MH  - Cannabinoids/*chemical synthesis/pharmacology/*therapeutic use
MH  - Concanavalin A/toxicity
MH  - Cytokines/*antagonists & inhibitors/*metabolism
MH  - Female
MH  - Hepatitis, Animal/metabolism/pathology/*prevention & control
MH  - Mice
MH  - Mice, Inbred BALB C
EDAT- 2003/12/04 05:00
MHDA- 2004/01/17 05:00
CRDT- 2003/12/04 05:00
PHST- 2003/12/04 05:00 [pubmed]
PHST- 2004/01/17 05:00 [medline]
PHST- 2003/12/04 05:00 [entrez]
AID - 64/6/1334 [pii]
AID - 10.1124/mol.64.6.1334 [doi]
PST - ppublish
SO  - Mol Pharmacol. 2003 Dec;64(6):1334-41. doi: 10.1124/mol.64.6.1334.