Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The HIV-1 co-receptor CCR5 has been thought a relevant target for small interfering RNA (siRNA)-based therapeutics. However, recent findings suggest that siRNA can stimulate innate cytokine responses in mammals. All siRNA agents tested were able to down-regulate the expression of CCR5, albeit with different efficiency (51-74% down-regulation), block HIV-induced syncytia formation between HIV-1 BaL-infected and uninfected CD4(+) cells or block single-round HIV-1 infection as measured by a luciferase reporter assay (46-83% inhibition). Conversely, siRNA directed against CCR5 did not affect replication of a vesicular stomatitis virus (VSV) pseudotyped virus, suggesting that inhibition of HIV replication was specific to CCR5 down-regulation. However, two of four siRNA tested were able to induce the production of interleukin (IL) IL-6 (sixfold induction) and IL-8 (ninefold induction) but no interferon (IFN)-alpha, IFN-beta, IFN-gamma, tumour necrosis factor (TNF)-alpha, monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, RANTES, IL-1beta, IL-10 or IL-12p70 cytokine induction was noted. In the absence of detectable IFN-alpha, IL-6 or IL-8 may represent markers of non-specific effects triggered by siRNA.
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PMID:Induction of interleukins IL-6 and IL-8 by siRNA. 1717 79

The vesicular stomatitis virus (VSV) causes encephalitis in mice when inoculated intranasally. The deer mouse (Peromyscus maniculatus), a native New World rodent, is also susceptible to VSV infection and develops similar central nervous system (CNS) lesions to those observed in other rodent species. Chemokines, such as regulated on activation, normal T-cell expressed and secreted (RANTES; CCL-5) and monocyte chemoattractant protein (MCP)-1 (CCL-2), which are important for chemotaxis and activation of inflammatory cells, are expressed during the course of VSV encephalitis. However, the role of CNS resident cells in chemokine expression is poorly characterized. Here, we show that during vesicular stomatitis New Jersey virus (VSNJV) encephalitis in deer mice, RANTES and MCP-1 are expressed only in the olfactory bulb (OB), where the virus was localized. This chemokine expression was followed by the influx of inflammatory cells to the OB later in the course of acute disease. Neurons, astrocytes and microglia expressed RANTES, while MCP-1 was expressed by neurons and astrocytes. Although astrocytes and microglia responded to VSNJV infection by expressing chemokines, neurons were the cell type that was predominantly infected. Therefore, infected neurons may have a critical role in initiating an immune response in the OB. The signalling between neurons and other CNS resident cells is most likely the mechanism by which astrocytes and microglia are activated during the course of VSV encephalitis.
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PMID:Expression Kinetics of RANTES and MCP-1 in the Brain of Deer Mice (Peromyscus maniculatus) Infected with Vesicular Stomatitis New Jersey Virus. 2778 May 75