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Autoimmune Diseases. (autoimmune + diseases)
Selected AbstractsCell adhesion molecules for targeted drug deliveryJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 9 2006Alison L. Dunehoo Abstract Rapid advancement of the understanding of the structure and function of cell adhesion molecules (i.e., integrins, cadherins) has impacted the design and development of drugs (i.e., peptide, proteins) with the potential to treat cancer and heart and autoimmune diseases. For example, RGD peptides/peptidomimetics have been marketed as anti-thrombic agents and are being investigated for inhibiting tumor angiogenesis. Other cell adhesion peptides derived from ICAM-1 and LFA-1 sequences were found to block T-cell adhesion to vascular endothelial cells and epithelial cells; these peptides are being investigated for treating autoimmune diseases. Recent findings suggest that cell adhesion receptors such as integrins can internalize their peptide ligands into the intracellular space. Thus, many cell adhesion peptides (i.e., RGD peptide) were used to target drugs, particles, and diagnostic agents to a specific cell that has increased expression of cell adhesion receptors. This review is focused on the utilization of cell adhesion peptides and receptors in specific targeted drug delivery, diagnostics, and tissue engineering. In the future, more information on the mechanism of internalization and intracellular trafficking of cell adhesion molecules will be exploited for delivering drug molecules to a specific type of cell or for diagnosis of cancer and heart and autoimmune diseases. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95: 1856,1872, 2006 [source] Inhibition of LFA-1/ICAM-1 and VLA-4/VCAM-1 as a therapeutic approach to inflammation and autoimmune diseasesMEDICINAL RESEARCH REVIEWS, Issue 2 2002Helena Yusuf-Makagiansar Abstract This review focuses on providing insights into the structural basis and clinical relevance of LFA-1 and VLA-4 inhibition by peptides and small molecules as adhesion-based therapeutic strategies for inflammation and autoimmune diseases. Interactions of cell adhesion molecules (CAM) play central roles in mediating immune and inflammatory responses. Leukocyte function-associated antigen (LFA-1, ,L,2, and CD11a/CD18) and very late antigen (VLA-4, ,4,1, and CD49d/CD29) are members of integrin-type CAM that are predominantly involved in leukocyte trafficking and extravasation. LFA-1 is exclusively expressed on leukocytes and interacts with its ligands ICAM-1, -2, and -3 to promote a variety of homotypic and heterotypic cell adhesion events required for normal and pathologic functions of the immune systems. VLA-4 is expressed mainly on lymphocyte, monocytes, and eosinophils, but is not found on neutrophils. VLA-4 interacts with its ligands VCAM-1 and fibronectin (FN) CS1 during chronic inflammatory diseases, such as rheumatoid arthritis, asthma, psoriasis, transplant-rejection, and allergy. Block-ade of LFA-1 and VLA-4 interactions with their ligands is a potential target for immunosuppression. LFA-1 and VLA-4 antagonists (antibodies, peptides, and small molecules) are being developed for controlling inflammation and autoimmune diseases. The therapeutic intervention of mostly mAb-based has been extensively studied. However, due to the challenging relative efficacy/safety ratio of mAb-based therapy application, especially in terms of systemic administration and immunogenic potential, strategic alternatives in the forms of peptide, peptide mimetic inhibitors, and small molecule non-peptide antagonists are being sought. Linear and cyclic peptides derived from the sequences of LFA-1, ICAM-1, ICAM-2, VCAM-1, and FN C1 have been shown to have inhibitory effects in vitro and in vivo. Finally, understanding the mechanism of LFA-1 and VLA-4 binding to their ligands has become a fundamental basis in developing therapeutic agents for inflammation and autoimmune diseases. © 2002 John Wiley& Sons, Inc. Med Res Rev, 22, No. 2, 146,167, 2002; DOI 10.1002/med.10001 [source] Evidence for the role of Th17 cell inhibition in the prevention of autoimmune diseases by anti-interluekin-6 receptor antibodyBIOFACTORS, Issue 1 2009Masahiko Mihara Abstract Deregulated production of interleukin-6 (IL-6) has been found in several chronic inflammatory autoimmune disorders, including rheumatoid arthritis (RA) and inflammatory bowel diseases. Treatment with tocilizumab, a humanized anti-human IL-6 receptor (IL-6R) antibody, significantly improved disease activity and inhibited the progression of joint destruction in RA patients, but the reason why IL-6 blockade causes improvement of RA is still unclear. In this review, we discuss the influence of anti-IL-6R antibody treatment on the differentiation of Th17 cells, which are thought to be involved in the pathogenesis of autoimmune diseases in animal models, present new results for the effect of anti-IL-6R antibody on the induction of Th17 cells in a mouse collagen-induced arthritis model, and come to the conclusion that anti-IL-6R antibody inhibited the differentiation of Th17 cells in mouse models. It is thought that this inhibitory action may contribute to the therapeutic effects of anti-IL-6R antibody in human autoimmune diseases. © 2009 International Union of Biochemistry and Molecular Biology, Inc. [source] Production of a recombinant cholera toxin B subunit-insulin B chain peptide hybrid protein by Brevibacillus choshinensis expression system as a nasal vaccine against autoimmune diabetesBIOTECHNOLOGY & BIOENGINEERING, Issue 7 2005Yoshikazu Yuki Abstract Mucosally induced tolerance is an attractive strategy for preventing or reducing autoimmune diseases. Here, we produced a recombinant CTB fusion protein linked with autoantigen T cell epitope of insulin B chain peptide 9,23 (C19S) at levels up to 200 mg/L culture media in Brevibacillus choshinensis secretion-expression system. Receptor-competitive assay showed that the CTB-insulin peptide binds to GM1 receptor almost equivalent degree as the native form of CTB. Non-obese diabetes (NOD) mice that spontaneously develop an insulin-dependent diabetes were nasally immunized with CTB-insulin peptide (5 µg) for three times. The nasal treatment significantly reduced the development of insulin-dependent diabetes and peptide specific DTH responses after systemic immunization with the insulin peptide B 9,23(C19S) in CFA. Nasal administration of as high as 50 µg of the peptide alone demonstrated a similar level of the disease inhibition. In contrast, all mice given 5 µg of the insulin peptide alone or 5 µg of insulin peptide with 25 µg of the free form of CTB did not lead to the suppression of diabetes development and DTH responses. Because molecular weight of the insulin peptide is about one tenth of that of the CTB-insulin peptide, the results demonstrate that the recombinant hybrid of autoantigen and CTB increased its tolerogenic potential for nasal administration by up 100-fold on molar base of autoantigen peptide. Taken together, nasally-induced tolerance by administration of the recombinant B.choshinensis -derived hybrid protein of CTB and autoantigen T cell-epitope peptide could be useful mucosal immunetherapy for the control of T cell-mediated autoimmune diseases. © 2005 Wiley Periodicals, Inc. [source] | |||||||||||||