ABSTRACT
15-deoxy-delta12,14-PGJ2(15d-PGJ2) is a natural ligand that activates the peroxisome proliferators-activated receptor (PPAR) gamma, a member of nuclear receptor family implicated in regulation of lipid metabolism and adipocyte differentiation. Recent studies have shown that 15d-PGJ2 is the potent anti-inflammatory agent functioning via PPARgamma-dependent and -independent mechanisms. Most postulated mechanisms for anti-inflammatory action of PPARgamma agonists are involved in inhibiting NF-kappaB signaling pathway. We examined the possibility that IL-6 signaling via the Jak-Stat pathway is modulated by 15d-PGJ2 in lymphocytes and also examined whether the inhibition of IL-6 signaling is dependent of PPARgamma. 15d-PGJ2 blocked IL-6 induced Stat1 and Stat3 activation in primary human lymphocytes, Jurkat cells and immortalized rheumatoid arthritis B cells. Inhibition of IL-6 signaling was induced rapidly within 15 min after treatment of 15d-PGJ2. Other PPARgamma-agonists, such as troglitazone and ciglitazone, did not inhibit IL-6 signaling, indicating that 15d-PGJ2 affect the IL-6-induced Jak-Stat signaling pathway via PPARgamma-independent mechanism. Although cycloheximide reversed 15d-PGJ2-mediated inhibition of Stat3 activation, actinomycin D had no effect on 15d-PGJ2-mediated inhibition of IL-6 signaling, indicating that inhibition of IL-6 signaling occur independent of de novo gene expression. These results show that 15d-PGJ2 specifically inhibit Jak-Stat signaling pathway in lymphocytes, and suggest that 15d-PGJ2 may regulate inflammatory reactions through the modulation of different signaling pathway other than NF-kappaB in lymphocytes.
Subject(s)
Humans , Arthritis, Rheumatoid/metabolism , Chromans/pharmacology , Cycloheximide/pharmacology , DNA-Binding Proteins/metabolism , Dactinomycin/pharmacology , Gene Expression Regulation , Hypoglycemic Agents/pharmacology , Interleukin-6/pharmacology , Jurkat Cells/metabolism , Lymphocytes/cytology , NF-kappa B/metabolism , PPAR gamma/metabolism , Phosphorylation , Prostaglandin D2/analogs & derivatives , Protein Synthesis Inhibitors/pharmacology , Signal Transduction , Thiazolidinediones/pharmacology , Trans-Activators/metabolismABSTRACT
HSV is known to cause infection at various parts in the human body such as skin, mouth, eyes, genital area, and brain. In this study, the authors showed the possibility of HSV replication in Jurkat, a human leukemic T lymphocytes. Although the yield production was very low when compared to the other 2 epithelial cells, Vero and HEp-2 cells, the yield production could enhance after PHA activation. Delayed viral protein expression was observed in Jurkat cells. This might be the reason for low production. However, the exactly mechanism is unknown. Replication of viruses have been examined in a number of cell systems and the duration of successive steps in the replication cycle depends upon the types of cells, the virus strain, and the multiplicity of infection.