It appears you don't have support to open PDFs in this web browser. To view this file, Open with your PDF reader
Abstract
Human HIV-1 infection leads inevitably to a chronic hyper-immune-activation. However, the nature of the targeted receptors and the pathways involved remain to be fully elucidated. We demonstrate that X4-tropic gp120 induced the production of TNF-α and IL-10 by monocytes through activation of a cell membrane receptor, distinct from the CD4, CXCR4, and MR receptors. Gp120 failed to stimulate IL-10 and TNF-α production by monocytes in Ca2+ free medium. This failure was total for IL-10 and partial for TNF-α. However, IL-10 and TNF-α production was fully restored following the addition of exogenous calcium. Accordingly, addition of BAPTA-AM and cyclosporine-A, fully and partially inhibited IL-10 and TNF-α respectively. The PKA pathway was crucial for IL-10 production but only partially involved in gp120-induced TNF-α. The PLC pathway was partially and equivalently involved in gp120-induced TNF-α and IL-10. Moreover, the inhibition of PI3K, ERK1/2, p38 MAP-kinases and NF-κB pathways totally abolished the production of both cytokines. In conclusion, this study revealed the crucial calcium signaling pathway triggered by HIV-1 gp120 to control the production of these two cytokines: TNF-α and IL-10. The finding could help in the development of a new therapeutic strategy to alleviate the chronic hyper-immune-activation observed in HIV-1 infected patients.
You have requested "on-the-fly" machine translation of selected content from our databases. This functionality is provided solely for your convenience and is in no way intended to replace human translation. Show full disclaimer
Neither ProQuest nor its licensors make any representations or warranties with respect to the translations. The translations are automatically generated "AS IS" and "AS AVAILABLE" and are not retained in our systems. PROQUEST AND ITS LICENSORS SPECIFICALLY DISCLAIM ANY AND ALL EXPRESS OR IMPLIED WARRANTIES, INCLUDING WITHOUT LIMITATION, ANY WARRANTIES FOR AVAILABILITY, ACCURACY, TIMELINESS, COMPLETENESS, NON-INFRINGMENT, MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. Your use of the translations is subject to all use restrictions contained in your Electronic Products License Agreement and by using the translation functionality you agree to forgo any and all claims against ProQuest or its licensors for your use of the translation functionality and any output derived there from. Hide full disclaimer
Details
1 INSERM, Toulouse, France; CNRS, Toulouse, France; University Paul-Sabatier, Toulouse, France
2 Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA, United States of America