D Reinhold

..Further in-vivo investigations, first in experimental models, will clarify, whether the inhibition of the enzymatic activity of DP IV could be a useful tool for therapeutic interventions in MS or other autoimmune diseases...

..This review summarizes the evidence for the role of both enzymes in T cell activation in vitro and in vivo and provides a rationale for using combined and dual peptidase inhibitors to treat autoimmune diseases like MS...

..Our data suggest that the N-terminal residues of HIV-1 Tat do interact directly with the active site of DP IV and that DP IV does mediate Tat's immunosuppressive effects...

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..In the following, we summarize the evidence for the role of both ectoenzymes in T cell activation in vitro and in vivo and provide a rationale for the use of combined or dual ectopeptidase inhibitors to treat autoimmune diseases like MS...

..1994, vol. 192, pp. 121-136). These data strongly suggest that Tat protein is a potent "natural" inhibitor of DP IV/CD26, and they support the hypothesis that DPIV plays a role in Tat's immunosuppressive activity...

..These data suggest the existence of endogenous immunomodulatory oligopeptides which influence immune cell proliferation and differentiation via DP IV as does HIV-1 Tat...

..The presented data fit into the hypothesis that inhibition of DP IV leads to the induction of TGF-beta(1), which in turn provokes an arrest of cell cycle in late G(1)...

..These data demonstrate that CD26 plays a role also in regulation of DNA synthesis of epidermal keratinocytes and that the enzymatic activity is required for mediating these effects...

..These findings demonstrate that bronchial and alveolar epithelial cells are capable of expressing cathepsin K, which could be of considerable importance for remodeling processes of the extracellular matrix in the lung...

..These data suggest that the N-terminal part of TXA2-R is an endogenous inhibitory ligand of DP IV and may modulate T cell activation via DP IV/CD26 inhibition...

..In summary our results strongly suggest that combined DPIV and APN inhibition by synthetic inhibitors represents a novel and efficient approach for the pharmacological therapy of IBD by triggering endogenous immunosuppressive mechanisms...

..Therefore, the simultaneous inhibition of these enzymes represents a promising strategy for the pharmacological therapy of T cell mediated diseases such as autoimmune disease, inflammation, allergy, and allograft rejection...

..42 nmol/L). Our results strongly suggest that different lung diseases do differ with regard to the released cytokines. TGF-beta1 probably plays a key role in regulation of pulmonary inflammation, particularly in pneumonia...

..These results strongly suggest a pathophysiologic role of neutrophil-derived serine proteases, particularly in regulation of the expression of functional IL-2 and IL-6 receptors at foci of inflammation...

..e. substrates and effectors, which are play the central role in DP IV/CD26 action in T cell growth and to understand the molecular mechanism of the early steps of this fundamental process...

..The lack of an evident phenotype could indicate that TRIM shares redundant functions with other transmembrane adaptors involved in regulating the immune response...

..The inactivation of IL-6 by neutrophil-derived serine proteases might act as a feedback mechanism terminating the IL-6-induced activation of neutrophils...

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..Our results indicate that high glucose-induced TGF-beta 1 production may suppress immune response by inhibiting the endogenous production of IL-2, IL-6 and IL-10...

..Targeting enzyme activity of DP IV and APN and their related molecules might be a novel approach for the treatment of acne, psoriasis or keloids...

..From these data we conclude that DP IV is involved in the regulation of proliferation of NK cells, whereas natural cytotoxicity seems to be regulated independently...

..The characterisation of subpopulations within the alveolar macrophages may be a useful tool for the monitoring of disease progression...

..Here we investigated for the first time the effects of DP-IV-related protease inhibitors and APN inhibitors on chronic inflammatory lung diseases...

..In summary, here, we demonstrate for the first time expression of attractin on monocytes and provide first data suggesting that drugs directed to DP IV-like enzyme activity could affect monocyte function via attractin inhibition...

..lt;6 ng/ml clearly correlates with a longer survival time. In conclusion, this study suggests that glioblastoma does secret TGF-beta2 in vivo and that TGF-beta2 may play an important role in glioblastoma patients...

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..These results demonstrate that SIT is a critical negative regulator of TCR-mediated signaling and finely tunes the signals required for thymic selection and peripheral T-cell activation...

..A major focus of this review are clinical aspects of the function of CD26 on hematopoietic cells and the potential usage of synthetic DP IV inhibitors as therapeutics in inflammatory disorders...

..In conclusion, atria of patients with permanent AF show evidence of calpain I activation that might contribute to structural remodeling and contractile dysfunction, whereas there is no evidence of activation of tissue cytokines...

..Data are presented suggesting that the antiproliferative effects of CIT extracts are due to their strong cytotoxic activity...

..Taken together, these data suggest that targeting alanyl aminopeptidases may be beneficial for psoriasis and other inflammatory skin disorders...

..Altogether, these data indicate an important role of PKB signals on control of TGF-beta1-mediated T cell responses and, thereby, on tolerizing and inflammatory immune processes...

..Inhibition of DP IV-like enzymatic activity may therefore represent a promising therapeutic approach for the treatment of fibrotic skin disorders and keloids...

..These data suggest that cathepsin K may play an important role in matrix remodeling of the lung under physiological and pathological conditions...

..The first active dual inhibitor, IP10.C8, has been developed by IMTM for the treatment of inflammatory skin diseases and has just entered the first phase II study...

..Further examinations are in progress to identify new physiologic, inhibitory DP IV ligands and to enlighten the mechanism underlying the DP IV-mediated effects...

..These results identify CD26/DP IV as a nonredundant inhibitory receptor controlling T cell activation and Th1-mediated autoimmunity, and may have important therapeutic implications for the treatment of autoimmune CNS disease...

..Autoimmune mechanisms are thought to play a role in the development of Crohn's disease, but the target antigens and the underlying pathways have not been sufficiently identified...

..Our results suggest the possibility of novel roles for these maternal effector cells in the pathogenesis or reduction of disease...

..The present investigation was aimed at examining which type of T cells has primary responsibility for this phenomenon...

..We conclude that aminopeptidase inhibitors support the suppressive activity as well as TGF-beta1 and FoxP3 expression of natural regulatory T-cells...

..v.IG therapy in MS. The variable amount of the potent anti-inflammatory TGF-beta isoforms within the i.v.IG preparations may exert a differentiated view regarding the manifold indications of i.v.IG therapy...

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..The factors that cause the actual fibrosis and the interaction between different cell types were investigated...

..Thus, these findings suggest that SKAP-HOM expression in DCs is required for the induction of an optimal immune response...

..Thus, the bee product propolis can be considered as a powerful natural anti-inflammatory medicine influencing different types of immune-responses probably via immunoregulatory T cells...

..These findings give new insights for the development of more potent and specific peptide-based DP IV inhibitors. Such inhibitors could be useful for the treatment of autoimmune and inflammatory diseases...

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