ヒトリンパ球混合培養反応における、AGE誘導性接着分子発見、サイトカイン産生、リンパ球増殖に対するヒスタミンの抑制効果の検討
| Autor: | Zhang, J, Takahashi, HK, Liu, K, Wake, H, Liu, R, Sadamori, H, Matsuda, H, Yagi, T, Yoshino, T, Mori, S, Nishibori, M |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Glycation End Products
Advanced Dose-Response Relationship Drug Down-Regulation Enzyme-Linked Immunosorbent Assay Flow Cytometry Intercellular Adhesion Molecule-1 Research Papers Cyclic AMP-Dependent Protein Kinases Monocytes Interferon-gamma Cyclic AMP Humans Receptors Histamine H2 Lymphocytes Cell Proliferation Histamine |
| Popis: | Post-transplant diabetes mellitus is a frequent complication among transplant recipients. Ligation of advanced glycation end products (AGEs) with their receptor on monocytes/macrophages plays important roles in the genesis of diabetic complications. The enhancement of adhesion molecule expression on monocytes/macrophages activates T-cells, reducing allograft survival. Out of four distinct AGE subtypes (AGE-2, AGE-3, AGE-4 and AGE-5), only AGE-2 and AGE-3 induced expression of intercellular adhesion molecules (ICAMs), output of cytokines and proliferation of lymphocytes, during the mixed lymphocyte reaction (MLR). Here we have assessed the role of histamine in the actions of AGEs during the MLR.Human peripheral blood cells were used in these experiments. Flow cytometry was used to examine the expression of the ICAM-1, B7.1, B7.2 and CD40. Production of the cytokine interferon-gamma, and levels of cAMP were determined by elisa. Lymphocyte proliferation was determined by [(3)H]-thymidine uptake.Histamine concentration dependently inhibited the action of AGE-2 and AGE-3. The actions of histamine were antagonized by an H(2)-receptor antagonist, famotidine, and mimicked by H(2)/H(4)-receptor agonists, dimaprit and 4-methylhistamine. The effects of histamine were reversed by a protein kinase A (PKA) inhibitor, H89, and mimicked by dibutyryl cAMP and an adenylate cyclase activator, forskolin.Histamine down-regulated AGE-2- and AGE-3-induced expression of adhesion molecules, cytokine production and lymphocyte proliferation via histamine H(2) receptors and the cAMP/PKA pathway. |
| Databáze: | OpenAIRE |
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