Human immunodeficiency virus 1 envelope proteins induce interleukin 1, tumor necrosis factor alpha, and nitric oxide in glial cultures derived from fetal, neonatal, and adult human brain.

Abstract

Although microglia are the only cells found to be productively infected in the central nervous system of acquired immunodeficiency disease syndrome (AIDS) patients, there is extensive white and gray matter disease nonetheless. This neuropathogenesis is believed to be due to indirect mechanisms other than infection with human immunodeficiency virus 1 (HIV-1). Cytokines and toxic small molecules have been implicated in the clinical and histopathological findings in CNS AIDS. Previously, we have demonstrated in rodent glial cultures the presence of biologically active epitopes of gp120 and gp41 that are capable of inducing interleukin 1 and tumor necrosis factor alpha. In this study, we map the HIV-1 envelope epitopes that induce nitric oxide, inducible nitric oxide synthase, interleukin 1, and tumor necrosis factor alpha in human glial cultures. Epitopes in the carboxy terminus of gp120 and the amino terminus of gp41 induce these proinflammatory entities. In addition, we compare HIV-1 infection and pathology in glial cells derived from human brain taken at different states of maturation (fetal, neonatal, and adult brain) in an effort to address some of the clinical and histological differences seen in vivo. This study demonstrates that, in the absence of virus infection and even in the absence of distinct viral tropism, human glia respond like rodent glia to non-CD4-binding epitopes of gp120/gp41 with cytokine and nitric oxide production. Differences among fetal, neonatal, and adult glial cells' infectivity and cytokine production indicate that, in addition to functional differences of glia at different stages of development, cofactors in vitro and in vivo may also be critical in facilitating the biological responses of these cells to HIV-1.

Anti-inflammatory action of type I interferons deduced from mice expressing interferon β

“…13,15 However, inappropriate expression of iNOS and overproduction of NO have adverse effects on the organism, these alterations participating in the onset of several pathologies such as various forms of neurodegeneration, chronic inflammation and autoimmune diseases. 18,19 For these reasons, the characterization of pathways involved in the negative regulation of macrophage activation constitutes a field of interest. 20 In this vein, inhibition by type I IFNs of iNOS expression has been described in macrophages stimulated in vitro with IFN-␥, and this has been explained in terms of the antagonism between type I and type II IFNs.…”

HIV-1 Envelope gp41 Peptides Promote Migration of Human FcεRI+ Cells and Inhibit IL-13 Synthesis Through Interaction with Formyl Peptide Receptors

“…Soluble gp41 has been shown to induce the production of proinflammatory cytokines such as TNF-␣ and IL-1 (17)(18)(19)(20)(21) and to increase the activity of nitric oxide synthetase in mononuclear phagocytes and glial cells (22). gp41 was also reported to suppress human lymphocyte proliferation (23) and to favor a Th2-type immune response by inducing IL-10 production in monocytes (24).…”

“…No natural FPRL2 agonists have been identified. However, it has been demonstrated that Helicobacter pylori peptide Hp (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) activates the monocyte via FPRL2 (34).…”

Phenotypic characterisation and infection of ovine microglial cells with Maedi-Visna Virus

“…Increased intrathecal expression of pro-in¯am-matory cytokines has been associated with neuropathological changes in primate lentivirus infections (Genis et al, 1992;Koka et al, 1995;Lane et al, 1996). Similarly, MVV infection has been shown to induce expression of TNFa within brain tissues (Craig et al, 1997).…”