Missé, Dorothée; Estève, Pierre-Olivier; Renneboog, Benoit; Vidal, Michel; Cerutti, Martine; St-Pierre, Yves 
ORCID: https://orcid.org/0000-0002-1948-2041; Yssel, Hans; Parmentier, Marc et Veas, Francisco
(2001).
HIV-1 glycoprotein 120 induces the MMP-9 cytopathogenic factor production that is abolished by inhibition of the p38 mitogen-activated protein kinase signaling pathway
Blood
, vol. 98
, nº 3.
pp. 541-547.
DOI: 10.1182/blood.v98.3.541.
Résumé
It has been previously shown that the HIV-1 envelope glycoprotein 120 (gp120) activates cell signaling by CXCR4, independently of CD4. The present study examines the involvement of different intracellular signaling pathways and their physiopathologic consequences following the CD4-independent interaction between CXCR4 or CCR5 and gp120 in different cell types: primary T cells, CD4(-)/CXCR4(+)/CCR5(+) T cells, or glioma cells. These interactions were compared with those obtained with natural ligands, stromal cell-derived factor 1 alpha (SDF-1alpha) (CXCL12) and macrophage inflammatory protein 1 beta (MIP-1beta) (CCL4) of their respective coreceptors. Thus, both p38 and SAPK/Jun N-terminal kinase mitogen-activated protein kinases (MAPKs) are activated on stimulation of these cells with either T- or M-tropic gp120, as well as with SDF-1alpha or MIP-1beta. In contrast, extracellular signal-related kinase 1 and 2 MAPKs are only activated by MIP-1beta but not by M-tropic gp120. Importantly, T- and M-tropic gp120 are able to induce the secretion of matrix metalloproteinase 9 (MMP-9), an extracellular metalloproteinase present in cerebrospinal fluid of patients with HIV-1 by T cells or glioma cells. Specific inhibition of MAPK p38 activation resulted in a complete abrogation of the induction of the MMP-9 pathogenic factor expression by gp120 or chemokines in both cell types. Because neurodegenerative features in acquired immune deficiency syndrome dementia may involve demyelinization by MMP-9, the specific targeting of p38 could provide a novel means to control HIV-induced cytopathogenic effects and cell homing to viral replication sites.
| Type de document: | Article |
|---|---|
| Mots-clés libres: | Chemokines; Cytokines; Interleukins; Signal Transduction |
| Centre: | Centre INRS-Institut Armand Frappier |
| Date de dépôt: | 14 avr. 2025 14:11 |
| Dernière modification: | 14 avr. 2025 14:11 |
| URI: | https://espace.inrs.ca/id/eprint/14974 |
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