HIV-1 glycoprotein 120 induces the MMP-9 cytopathogenic factor production that is abolished by inhibition of the p38 mitogen-activated protein kinasesignaling pathway

Citation
D. Misse et al., HIV-1 glycoprotein 120 induces the MMP-9 cytopathogenic factor production that is abolished by inhibition of the p38 mitogen-activated protein kinasesignaling pathway, BLOOD, 98(3), 2001, pp. 541-547
Citations number
59
Categorie Soggetti
Hematology,"Cardiovascular & Hematology Research
Journal title
BLOOD
ISSN journal
00064971 → ACNP
Volume
98
Issue
3
Year of publication
2001
Pages
541 - 547
Database
ISI
SICI code
0006-4971(20010801)98:3<541:HG1ITM>2.0.ZU;2-Y
Abstract
It has been previously shown that the HIV-1 envelope glycoprotein 120 (gp12 0) activates cell signaling by CXCR4, independently of CD4. The present stu dy examines the involvement of different intracellular signaling pathways a nd their physiopathologic consequences following the CD4-independent intera ction between CXCR4 or CCR5 and gp120 in different cell types: primary T ce lls, CD4(-)/ CXCR4(+)/CCR5(+) T cells, or glioma cells. These interactions were compared with those obtained with natural ligands, stromal cell-derive d factor 1 alpha (SDIF-1 alpha) (CXCL12) and macrophage inflammatory protei n 1 beta (MIP-1 beta) (CCL4) of their respective coreceptors. Thus, both p3 8 and SAPK/Jun N-terminal kinase mitogen-activated protein kinases (MAPKs) are activated on stimulation of these cells with either T- or M-tropic gp12 0, as well as with SDF-1 alpha. or MIP-1 beta. In contrast, extracellular s ignal-related kinase 1 and 2 MAPKs are only activated by MIP-1 beta but not by M-tropic gp120. Importantly, T- and M-tropic gp120 are able to induce t he secretion of matrix metalloproteinase 9 (MMP-9), an extracellular metall oproteinase present In cerebrospinal fluid of patients with HIV-1 by T cell s or glioma cells. Specific inhibition of MAPK p38 activation resulted in a complete abrogation of the induction of the MMP-9 pathogenic factor expres sion by gp120 or chemokines in both cell types. Because neurodegenerative f eatures in acquired Immune deficiency syndrome dementia may involve demyeli nization by MMP-9, the specific targeting of p38 could provide a novel mean s to control HIV-induced cytopathogenic effects and cell homing to viral re plication sites.