Scientific Publications by FDA Staff
J Leukoc Biol 2010 May;87(5):915-24
Lipopolysaccharide suppresses HIV-1 replication in human monocytes by protein kinase C-dependent heme oxygenase-1 induction.
Devadas K, Hewlett IK, Dhawan S
LPS is an important component of the Gram-negative bacteria cell wall. It activates monocytes and induces multiple host immune and inflammatory responses. Interestingly, in spite of inducing host-inflammatory responses, LPS also protects monocyte-derived macrophages from infection by HIV-1. In this report, we have shown that LPS treatment of human monocyte-derived macrophages markedly suppressed HIV-1 replication, even on addition to infected cells 24 h after infection. Inhibition of HIV-1 replication was associated with PKC-dependent induction of HO-1, a cytoprotective enzyme known to catabolize heme. Pretreatment with the PKC inhibitor Go 6976 not only substantially inhibited LPS-mediated induction of HO-1 but also attenuated LPS-induced suppression of HIV replication. Significant reduction of HIV replication by inhibitors of JNK, NF-kappaB, and PI3K was independent of a LPS-mediated anti-HIV effect. Specificity of HO-1 was confirmed by substantial reversal of LPS-induced viral replication by pretreatment of cells with SnPP IX, an inhibitor of HO-1 enzyme activity. These results demonstrate a previously undefined function of HO-1 as a host defense mechanism in LPS-mediated inhibition of HIV-1 replication.
|Category: Journal Article|
|PubMed ID: #20061555||DOI: 10.1189/jlb.0307172|
|Includes FDA Authors from Scientific Area(s): Biologics|
|Entry Created: 2011-10-04||Entry Last Modified: 2012-08-29|