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 - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Blood Année : 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

Pierre-Olivier Estève
  • Fonction : Auteur
Benoit Renneboog
  • Fonction : Auteur
Michel Vidal
Martine Cerutti
  • Fonction : Auteur
Yves St Pierre
  • Fonction : Auteur
Hans Yssel
Marc Parmentier
  • Fonction : Auteur
Francisco Veas
  • Fonction : Auteur

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 α (SDF-1α) (CXCL12) and macrophage inflammatory protein 1 β (MIP-1β) (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-1α or MIP-1β. In contrast, extracellular signal-related kinase 1 and 2 MAPKs are only activated by MIP-1β 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.

Dates et versions

hal-02959990 , version 1 (07-10-2020)

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Citer

Dorothée Missé, Pierre-Olivier Estève, Benoit Renneboog, Michel Vidal, Martine Cerutti, et al.. 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, 2001, 98 (3), pp.541-547. ⟨10.1182/blood.v98.3.541⟩. ⟨hal-02959990⟩
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