The protein phosphatase inhibitor XXXX stimulates chemokine production by @entity1 synovial cells.

@entity1 @entity650 @entity5737 @entity29478 @entity5 @entity310 @entity2842 @entity1192 @entity563 @entity1889 @entity687
Cultured @entity1 synovial fibroblasts express mRNA for the chemotactic cytokines (chemokines) @entity687 ( @entity687 ), @entity2842 ( @entity2842 ) and regulated upon activation normal T-cell expressed and presumably secreted ( @entity5737 ), when stimulated with @entity1192 or @entity5 necrosis factor alpha ( @entity310 ). @entity29478 , a potent type 1/2A protein @entity563 / @entity1889 phosphatase inhibitor, was used to examine the role of protein phosphatases in the regulation of chemokine gene expression. @entity29478 (1 nM) mimicked @entity1192 by inducing @entity687 and @entity2842 mRNA expression in synovial cells. @entity687 mRNA was induced over a similar time period (1-6 h) in response to @entity1192 or @entity29478 , whereas @entity2842 mRNA was induced more rapidly (1-2 h) by @entity29478 than by @entity1192 (4-6 h). Expression of @entity5737 mRNA occurred in response to @entity310 , but could not be induced by stimulation with @entity29478 alone. These results suggest that inhibition of protein phosphatase type 1/2A may have a differential role in the regulation of the expression of each of the chemokine genes. Synovial fibroblasts also secreted @entity687 and @entity650 peptide when stimulated with either @entity1192 / @entity310 or @entity29478 . The amount of @entity687 and @entity650 peptide produced in response to @entity29478 was significantly increased above that produced by untreated synovial cells, though it was much less than the amount induced by @entity1192 or @entity310 . @entity29478 also acted synergistically with @entity1192 or @entity310 to cause a 2-fold potentiation of @entity1192 - or @entity310 -induced @entity687 mRNA and peptide and @entity5737 mRNA expression. These results suggest that although inhibition of a protein phosphatase may be able to regulate the magnitude of @entity1192 -induced chemokine gene expression, the @entity1192 signal transduction pathway involves components in addition to phosphatase inhibition, possibly including the activation of a protein kinase, the action of which may be opposed by a protein phosphatase inhibited by @entity29478 .
