S-nitrosoglutathione modulates CXCR4 and ICOS expression.
The expression of CXCR4, a membrane protein which is involved in the entry of HIV-1, is down-modulated from the cell surface by Phorbol 12-myristate 13-acetate (PMA) and the Ca+ ionophore, Ionomycin. Inducible co-stimulator (ICOS), which contributes to lymphocyte proliferation, is up-regulated by PMA/Ionomycin. We examined the influence of S-nitrosoglutathione (SNG), an inhibitor of Vacuolar H+-ATPase (V-ATPase), on the expression of CXCR4 and ICOS in PMA/Ionomycin-treated peripheral mononuclear cells (PBMC), and of CXCR4 alone in lymphoid cell lines. In this report, we show that SNG interferes with both effects of PMA/Ionomycin, namely CXCR4 down-regulation and ICOS up-regulation. These studies imply opposing roles of V-ATPase in the regulation of CXCR4 and ICOS. The influence of SNG in modulating the susceptibility of T cells to HIV-1 and on their immune responses needs further investigation.
Yamamoto
Yoshihiko
Y
Department of Pediatrics, North Shore-LIJ Research Institute, Immunology & Inflammation Center of Excellence, New York University School of Medicine, Manhasset, NY 11030, USA. yoyamamo@onh.go.jp
Pahwa
Rajendra
R
Pahwa
Savita
S
D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein; D019169:Jurkat Cells; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D019718:Receptors, CXCR4 / Q000096:biosynthesis* / Q000235:genetics*; D026422:S-Nitrosoglutathione / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
D000945:Antigens, Differentiation, T-Lymphocyte; C486264:Cxcr4 protein, rat; C556692:ICOS protein, human; C556695:Icos protein, rat; D060889:Inducible T-Cell Co-Stimulator Protein; D020030:Nitric Oxide Donors; D019718:Receptors, CXCR4; D026422:S-Nitrosoglutathione