Leflunomide or methotrexate plus subcutaneous tumour necrosis factor-alpha (TNF-alpha) blocking agents in rheumatoid arthritis

2013 ◽  
Author(s):  
Maurizio Benucci
1998 ◽  
Vol 20 (2) ◽  
pp. 221-231 ◽  
Author(s):  
WR Hansen ◽  
T Sato ◽  
MD Mitchell

We have evaluated the mechanism by which tumour necrosis factor-alpha (TNF-alpha) induces increased prostaglandin (PG) biosynthesis in amnion-derived WISH cells. WISH cells were treated with 50 ng/ml TNF-alpha or vehicle for 0-24 h. PGE2 production was stimulated by TNF-alpha within 2 h and continued to accumulate for at least 24 h. Increased prostaglandin endoperoxide H synthase (PGHS)-2 mRNA expression was evident within 30 min and was highest by 1 h, returning to unstimulated levels by 2 h. The PGHS-2 mRNA was re-induced at 8 h and was also elevated at 16 h. Immunoreactive PGHS-2 protein was nearly undetectable in control cells. However, within 30 min of TNF-alpha treatment, PGHS-2 protein was elevated and was induced for at least 16 h suggesting rapid production of both the PGHS-2 mRNA and protein. Transcription run-on assays indicated that the initial increase in the PGHS-2 mRNA was due to a 20-fold increase in the rate of transcription. The PGHS-2 mRNA decayed with an apparent half-life of 1 h in TNF-alpha-stimulated WISH cells. Induction of PGHS-2 expression proceeded in the presence of 10 microg/ml cycloheximide which agrees with the classification of PGHS-2 as an immediate early gene. These results indicate that a bi-phasic induction of the PGHS-2 mRNA is due, in part, to an initial transcriptional activation which results in rapid and continued synthesis of the PGHS-2 protein. This may be a unique characteristic of amnion cells which may be partially responsible for increased PG concentrations in the amniotic fluid during infection-associated preterm labour.


1994 ◽  
Vol 12 (2) ◽  
pp. 127-133 ◽  
Author(s):  
Victor A. Danis ◽  
Michelle Millington ◽  
Valentine Hyland ◽  
Ron Lawford ◽  
Qirong Huang ◽  
...  

The frequency of the uncommon allele (TNF2) of a polymorphism in the promoter region of the tumour necrosis factor alpha (TN Fα) gene in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) was found to be 3 times that of the normal anglo-saxon population. In SLE patients, this allele was strongly associated with HLA-DR3 expression and was also more frequent in patients who did not have malar rash. Functional studies of normal monocyte cytokine production in vitro showed that this genotype was associated with increased IL-1α protein production but there were no differences in the production of TNFα protein.


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