HIV1 protease inhibitors selectively induce inflammatory chemokine expression in primary human osteoblasts.
HIV-infected patients are at increased risk of decreased bone mineral density. Several studies have implicated antiretroviral therapy as a contributor to the decreased bone mineral density seen in treated HIV-1 patients. Whilst the exact molecular mechanisms underlying decreased bone density remain to be elucidated, inflammation has been postulated to be an important pathogenomic mechanism. In this study, we have explored primary human osteoblast gene expression in response to protease inhibitors (PIs), by oligonucleotide microarray analysis. A list of dysregulated genes, correlated with the inflammatory response, increased significantly after NFV and RTV exposure. Analysis of gene and protein expression determined a selectively increase of the pro-inflammatory cytokines monocyte chemoattractant protein (MCP)-1 and interleukin-8 (IL-8) following exposure to a pharmacological concentration of NFV and RTV. These data suggested that generation of local inflammatory cascades may contribute to the development of decreased bone mineral density in highly active antiretroviral therapy (HAART)-treated HIV patients.
Malizia
Andrea P
AP
General Clinical Research Unit, School of Medicine and Medical Sciences, University College Dublin, Ireland.
Vioreanu
Mihai H
MH
Doran
Peter P
PP
Powderly
William G
WG
D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D019888:Nelfinavir / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D019438:Ritonavir / Q000494:pharmacology*
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D018925:Chemokines; D017320:HIV Protease Inhibitors; D016209:Interleukin-8; D019888:Nelfinavir; D019438:Ritonavir