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

The effects of interferon (IFN) on Fc receptor-mediated phagocytosis, intracellular cAMP levels, antiviral activity, and growth inhibition were analyzed in a cloned macrophage-like cell line, J774.2, and variants derived from it. Purified IFN increased Fc receptor-mediated phagocytosis in J774.2 cells, and in cAMP-responsive nonphagocytic variants but was without effect in cAMP-unresponsive nonphagocytic variants, in adenylate cyclase-deficient variants, and in cAMP-dependent protein kinase-deficient variants. Under conditions in which IFN augmented phagocytosis, it increased intracellular levels of cAMP. Parental cells were highly sensitive to IFN-mediated growth inhibition. In contrast, cAMP-dependent protein kinase-deficient variants were only 1/100th as sensitive to growth inhibition by IFN. All cell lines tested, both responsive and unresponsive to cAMP, were equally protected by IFN against infection with vesicular stomatitis virus, demonstrating that the antiviral state was independent of cAMP. These results indicate that, in transformed macrophages, stimulation of phagocytosis and inhibition of growth by IFN are mediated through intracellular cAMP, whereas the antiviral state induced by IFN is independent of cAMP.
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PMID:Genetic analysis of the role of cAMP in mediating effects of interferon. 617 3

Several derivatives of K-252a, a protein kinase inhibitor isolated from Nocardiopsis sp., were investigated for their effects on the replication of vesicular stomatitis virus (VSV) in BHK-21 cell cultures. Among those we tested, KT5926, which preferentially inhibits the myosin light chain kinase (MLCK), suppressed the viral replication by 95-99% at 15 microM. K-252a, which inhibits a broad spectrum of cellular protein kinase, similarly affected the viral replication. Other derivatives, KT5720 and KT5823, that are known to inhibit the cAMP-dependent protein kinase (PKA) and cGMP-dependent protein kinase (PKG), respectively, did not suppress VSV replication even at a high concentration as 15 microM. None of these inhibitors affected the Sindbis virus replication in BHK-21 cells under similar assay conditions as used for VSV. KT5926 and K-252a seemed to affect the VSV replication at the step(s) after the viral invasion, resulting in decreased viral RNA synthesis. Neither substance inhibited cellular casein kinase (CK) II which is known to be involved in phosphorylation of the nonstructural (NS) protein, a non-catalytic subunit of the viral RNA polymerase. These results suggest that the inhibition of VSV replication by KT5926 and K-252a is not a secondary effect due to generalized suppression of host cell activities, and that the VSV replication requires the KT5926-sensitive function(s) in the cell which would be performed by an enzyme(s) other than CK II.
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PMID:Studies on the antiviral activity of protein kinase inhibitors against the replication of vesicular stomatitis virus. 755 Jan 28