An in vivo observation of close contact rolipram and arthritis T cells and macrophages in the RA synovial lining supports this observation Recently, IL was found to be present at high concentrations in RA synovium A product of synovial macrophages and fibroblasts, IL acts as rolipram and arthritis chemoattractant 15 and growth factor for T lymphocytes, resembling IL-2 in many of its biological functions Other major effects of IL on T cells include: This observation further supports the hypothesis that T cells play an important role in the onset and rolipram and arthritis of pathogenic events in RA and suggests that pharmacological agents that block the ILmediated stimulation of T cells may be of clinical use in treating RA.
Rolipram, rolipram and arthritis, a cAMP-specific phosphodiesterase inhibitor 24has been shown to ameliorate collagen-induced arthritis in animal models and is under consideration as a possible therapeutic agent for RA However, the mechanism of action and target cell population of rolipram in the synovium has not been elucidated, rolipram and arthritis.
Rolipram is a specific inhibitor of type IV phosphodiesterase, an enzyme that catalyzes the breakdown of cAMP. Mononuclear cells were isolated rolipram and arthritis heparinized venous blood of healthy donors by Ficoll-paque density gradient centrifugation. The dose-response for inhibition of proliferation is shown in Fig. Coculture experiments were performed as previously described Briefly, T cells were cultured for 3 days in complete medium in the presence or absence of T cell activators and cAMP modulators.
These paraformaldehyde-fixed T cells were washed thrice and then cocultured with U cells at a ratio of 7: Results obtained with various Abs were always compared with their respective isotype control Abs, rolipram and arthritis. Briefly, an equal number of human peripheral blood T cells was treated with the indicated reagents for 10 min. The cells were washed twice in cold PBS.
Percent activated PKA was calculated as: The T cells were then fixed with paraformaldehyde and cocultured with U cells at a 7: Statistical analysis was similar to Fig. Two additional controls were performed. However, rolipram and arthritis, addition of PMA alone is known to produce a limited or partial activation of T lymphocytes. This partial activation of T cells produces a phenotype with increased expression of surface molecules, such as CD69, LFA-1, and ICAM-1 2134but does not induce a high rate of proliferation.
PMA has also been shown to up-regulate the IL receptor These T cells were then cocultured for 72 h with U cells. As described in Materials and MethodsT cells were washed and cocultured with U cells for 48 h. To determine which parameters of IL induced activation of T cells are being blocked by rolipram and CPT-cAMP, changes in proliferation measured by thymidine incorporation and cell surface molecules measured by flow cytometry were monitored in the presence and absence of IL Figs.
One of three independent experiments is presented, rolipram and arthritis. To determine whether rolipram and CPT-cAMP effect the expression of these molecules on ILstimulated T cells, the surface concentration of these molecules was monitored by flow cytometry.
Neither agent had any effect on CD3 expression, suggesting the these agents selectively inhibit the expression only of cell surface markers that are up-regulated during activation. ARolipram and arthritis lines represent untreated control cultures, while blue lines represent T cells treated with IL the blue and black lines are also repeated in all three panels to allow for easy comparison with cells treated with CPT-cAMP and rolipram.
The isotype-matched controls green line, rolipram and arthritis, left column did not change with treatments. B and CLight solid lines represent control cultures without any agent, while dark solid lines are for T cells treated with IL left column and repeated in middle and right column. CPT-cAMP or rolipram treatments middle and right columns, respectively are indicated by closely spaced dotted lines, rolipram and arthritis.
The loosely spaced dotted lines are isotype controls left column. A representative of plans discone antenna experiments is shown. A summary of data from all four experiments is shown in D.
Even under these conditions, rolipram and CPT-cAMP effectively inhibited the expression of all three molecules compare dotted line with dark solid line in Fig. PKA activity was then measured in another name for vitamin c or absence of cAMP in the reaction mixture to determine the percent activation level Fig. Rolipram, a phosphodiesterase inhibitor, has been shown to ameliorate collagen-induced arthritis in mice 25 Thus, the U cells can be cocultured with ILstimulated T cells without the possibility that the macrophages will be affected by IL Inhibition of T cell proliferation by cAMP analogues in vitro is well known CPT-cAMP, and, to a lesser extent, rolipram, were capable of reducing the increased expression of these surface molecules Fig.
We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Skip to main content. KasyapaCarrie L. Stentzrolipram and arthritis, Michael P. Davey and Daniel W. J Immunol Rolipram and arthritis 1,5.
Preparation of cells Mononuclear cells were isolated from heparinized venous blood of healthy rolipram and arthritis by Ficoll-paque density gradient centrifugation. T cell-macrophage coculture Coculture experiments were performed as previously described Role of cytokines in rheumatoid arthritis.
Mechanism of joint destruction in rheumatoid arthritis. The role of macrophages in chronic arthritis. How important are Rolipram and arthritis cells in chronic rheumatoid synovitis?
The shared epitope hypothesis: Contact with T cells modulates monocyte IL production: An immunohistological analysis of lymphocyte subpopulations and their microenvironment in the synovial membranes of patients with rheumatoid arthritis using monoclonal antibodies.
The role of interleukin in T-cell migration rolipram and arthritis activation in rheumatoid arthritis. Chemoattraction of human blood T lymphocytes by interleukin Interleukin-2, interleukin, and their receptors.
Interleukin induces adhesion receptor redistribution in T lymphocytes. Activation of naive and memory T cells by interleukin Interleukin 15 is produced by endothelial cells and increases the transendothelial migration of T cells in vitro and in the SCID mouse-human rheumatoid arthritis model in vivo. T cell activation via Leu CD Amelioration of collagen II-induced arthritis in rats by the type IV phosphodiesterase inhibitor Rolipram.
Suppression of IL production by phosphodiesterase inhibition rolipram and arthritis murine endotoxemia is IL independent. Enhanced tumor necrosis factor suppression and cyclic adenosine monophosphate accumulation by combination of phosphodiesterase inhibitors and prostanoids. Pentoxifylline inhibits human T-cell adhesion to dermal endothelial cells. Evaluation of the role of cytokines in autoimmune disease: T-cell-dependent pathways in rheumatoid arthritis. IL functions as a potent autocrine regulator of macrophage proinflammatory cytokine production: The adenylate cyclase-cAMP-protein kinase A pathway and regulation of the immune response.
The Journal of Immunology Vol. Thank you for your interest in spreading the word about The Journal of Immunology. DaveyDaniel W. The Journal of Immunology September 1,5. Tweet Widget Facebook Like. Identification of novel small molecule inducers of endothelium-driven innate immunity