Because a large number of mouse lines in which Cre recombinase is expressed in a tissue or a cell type-specific manner have been reported and are available, it is likely that the use of these bioresources with specific promoters expands the usefulness of our inducible knockdown system. For instance, this approach enables knockdown in a specific cortical layer or in a specific neuronal subtype. We examined whether the pT2K-TBI-shRNAmir vectors were integrated into the chromosomes. If the vectors were not integrated into the chromosome, these vectors were re-distributed into two daughter cells after mitosis. Eventually the number of these vectors in individual cells should become very small. In contrast, in the cells harboring such vectors in their chromosomes, these vectors should be retained after cell division. Proinflammatory cytokines present in the rheumatic milieu, such as tumor necrosis factor, interleukin IL-6 are prominent inducers of MPGES1.As illustrated in Fig. 2, CD20 positive B cells and CD138 plasma cells have different areas of distribution compared to MPGES1 expressing cells, with virtually no overlapping. In turn, by interacting with FLS, PGE2 promotes release of IL-6 and matrix metalloproteinase-1, Chloramine-T thereby further sustaining a pathogenic circle. COX-2 derived PGE2 also plays a central role in the humoral responses, since blocking this pathway Veratramine substantially decreases antibody production. PGE2 regulates B cell proliferation and activation as well as survival. This implies a possible role for PGE2 as a mediator of B cell immune responses in RA. To investigate this hypothesis, we studied the expression of PGE2related enzymes in SF and peripheral blood -derived B cells of RA patients. Furthermore, we hypothesised that depleting B cells could change synovial immune interactions, reduce cytokine levels and decrease disease activity in the inflamed joint. These effects can in turn affect the PGE2 biosynthetic pathway and further contribute to decline local inflammation and clinical benefit. In this sense, it has been reported that B cells are essential in sustaining PGE2 production by lung macrophages.