Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mononuclear phagocytes (monocytes, macrophages, and dendritic cells) play major roles in human immunodeficiency virus (HIV) persistence and disease pathogenesis. Macrophage antigen presentation and effector cell functions are impaired by HIV-1 infection. Abnormalities of macrophage effector cell function in bone marrow, lung, and brain likely result as a direct consequence of cellular activation and HIV replication. To further elucidate the extent of macrophage dysfunction in HIV-1 disease, a critical activation-specific regulatory molecule, nitric oxide (NO.), which may contribute to diverse pathology, was studied. Little, if any, NO. is produced by uninfected human monocytes. In contrast, infection with HIV-1 increases NO. production to modest, but significant levels (2-5 microM). Monocyte activation (with lipopolysaccharide, tumor necrosis factor alpha, or through interactions with astroglial cells) further enhances NO. production in HIV-infected cells, whereas its levels are diminished by interleukin 4. These results suggest a possible role for NO. in HIV-associated pathology where virus-infected macrophages are found. In support of this hypothesis, RNA encoding the inducible NO synthase (iNOS) was detected in postmortem brain tissue from one pediatric AIDS patient with advanced HIV encephalitis. Corresponding iNOS mRNA was not detected in brain tissue from five AIDS patients who died with less significant brain disease. These results demonstrate that HIV-1 can influence the expression of NOS in both cultured human monocytes and brain tissue. This newly described feature of HIV-macrophage interactions suggests previously unappreciated mechanisms of tissue pathology that result from productive viral replication.
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PMID:Regulation of nitric oxide synthase activity in human immunodeficiency virus type 1 (HIV-1)-infected monocytes: implications for HIV-associated neurological disease. 753 Jul 62

HIV encephalitis (HIVE) is a neurodegenerative disease seen in approximately one in four terminally infected patients. Macaques infected with the simian immunodeficiency virus develop encephalitis (SIVE) very similar to the human disease. Neurodegeneration in both these conditions occurs from the effects of toxic viral proteins and neurotoxins derived from activated brain macrophages. Activated macrophages in the brain of macaques with SIVE can be labeled in vivo using positron emission tomography (PET) using PK11195, a ligand that binds the peripheral benzodiazepine receptor (PBR). However, the functional significance and mechanisms mediating increased PK11195 binding in activated brain macrophages are not known. Using post mortem tissues from macaques with SIVE and macrophages cell cultures activated with lipopolysaccharide (LPS), we show that [(3)H](R)-PK11195 binding is increased in activated macrophages. Increased [(3)H](R)-PK11195 binding in LPS-activated macrophages was reversed by pharmacologically inhibiting class III phosphatidylinositol-3 kinase (PI3-kinase), but was not altered by inhibiting the mitogen-activated protein kinase (MAP-kinase) pathway. Our results suggest that activated macrophages in lentiviral encephalitis show increased [(3)H](R)-PK11195 binding in a PI3-kinase-dependent fashion which may help elucidate the function of PBR in activated brain macrophages in HIVE and other neuroinflammatory diseases.
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PMID:Activated macrophages in HIV encephalitis and a macaque model show increased [3H](R)-PK11195 binding in a PI3-kinase-dependent manner. 1788 71