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Immunology, 2000
We report that interleukin (IL)-4 and IL-10 can signi®cantly up-or down-regulate CXC chemokine re... more We report that interleukin (IL)-4 and IL-10 can signi®cantly up-or down-regulate CXC chemokine receptor 4 (CXCR4) expression on CD4 + T lymphocytes, respectively. Stromal cell-derived factor-1a (SDF-1a)-induced CD4 + T-lymphocyte chemotaxis was also correspondingly regulated by IL-4 and IL-10. IL-4 and IL-10 up-or down-regulated CXCR4 mRNA expression in CD4 + T lymphocytes, respectively, as detected by real-time quantitative reverse transcription±polymerase chain reaction (RT±PCR). Scatchard analysis revealed a type of CXCR4 with af®nity (K d < 6 . 3 nM), and < 70 000 SDF-1a-binding sites per cell, among freshly isolated CD4 + T lymphocytes, and two types of CXCR4 with different af®nities (K d1 < 4 . 4 nM and K d2 < 14 . 6 nM), and a total of < 130 000 SDF-1a-binding sites per cell, among IL-4-stimulated CD4 + T lymphocytes. The regulation of CXCR4 expression in CD4 + T lymphocytes by IL-4 and IL-10 could be blocked by a selective inhibitor of protein kinase (staurosporine) or by a selective inhibitor of cAMP-and cGMPdependent protein kinase (H-8), indicating that these cytokines regulate CXCR4 on CD4 + T lymphocytes via both cAMP and cGMP signalling pathways. The fact that cyclosporin A or ionomycin were able to independently change the CXCR4 expression and block the effects of IL-4 and IL-10 on CXCR4 expression implied that the capacity of IL-4 and IL-10 to regulate CXCR4 on CD4 + T lymphocytes is not linked to calcium-mobilization stimulation. These results indicate that the effects of IL-4 and IL-10 on the CXCR4±SDF-1 receptor±ligand pair may be of particular importance in the cytokine/chemokine environment concerning the in¯ammatory processes and in the progression of human immunode®ciency virus (HIV) infection.
Immunology, 2000
We report that interleukin (IL)-4 and IL-10 can signi®cantly up-or down-regulate CXC chemokine re... more We report that interleukin (IL)-4 and IL-10 can signi®cantly up-or down-regulate CXC chemokine receptor 4 (CXCR4) expression on CD4 + T lymphocytes, respectively. Stromal cell-derived factor-1a (SDF-1a)-induced CD4 + T-lymphocyte chemotaxis was also correspondingly regulated by IL-4 and IL-10. IL-4 and IL-10 up-or down-regulated CXCR4 mRNA expression in CD4 + T lymphocytes, respectively, as detected by real-time quantitative reverse transcription±polymerase chain reaction (RT±PCR). Scatchard analysis revealed a type of CXCR4 with af®nity (K d < 6 . 3 nM), and < 70 000 SDF-1a-binding sites per cell, among freshly isolated CD4 + T lymphocytes, and two types of CXCR4 with different af®nities (K d1 < 4 . 4 nM and K d2 < 14 . 6 nM), and a total of < 130 000 SDF-1a-binding sites per cell, among IL-4-stimulated CD4 + T lymphocytes. The regulation of CXCR4 expression in CD4 + T lymphocytes by IL-4 and IL-10 could be blocked by a selective inhibitor of protein kinase (staurosporine) or by a selective inhibitor of cAMP-and cGMPdependent protein kinase (H-8), indicating that these cytokines regulate CXCR4 on CD4 + T lymphocytes via both cAMP and cGMP signalling pathways. The fact that cyclosporin A or ionomycin were able to independently change the CXCR4 expression and block the effects of IL-4 and IL-10 on CXCR4 expression implied that the capacity of IL-4 and IL-10 to regulate CXCR4 on CD4 + T lymphocytes is not linked to calcium-mobilization stimulation. These results indicate that the effects of IL-4 and IL-10 on the CXCR4±SDF-1 receptor±ligand pair may be of particular importance in the cytokine/chemokine environment concerning the in¯ammatory processes and in the progression of human immunode®ciency virus (HIV) infection.