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)

Among the pleiotropic effects of human interferon are the inhibition of viral replication, the activation of natural killer cells, and the inhibition of cellular growth. Oxyphenbutazone, a nonsteroidal antiinflammatory agent, is a potent inhibitor of the antiviral activity of human alpha and beta interferons as determined by cytopathic effect and vesicular stomatitis virus synthesis and release in human foreskin fibroblasts. The inhibition of interferon activity is dose dependent with maximal inhibition at 25-50 microM and minimal inhibition at 1 microM. In contrast, oxyphenbutazone at concentrations as high as 100 microM has no effect on the activation of natural killer cells by human interferon. Similarly, oxyphenbutazone has no inhibitory effect on interferon-induced antigrowth activity in the human breast carcinoma cell line MDA-MB-231. This cell line is sensitive to oxyphenbutazone inhibition of interferon-induced antiviral activity in vitro. In another human cell line, the vulvar carcinoma A431, oxyphenbutazone apparently augments the antigrowth activity of interferon. Although oxyphenbutazone inhibits the fatty acid cyclooxygenase enzyme in these systems, other inhibitors of cyclooxygenase fail to inactivate the antiviral activity of human interferon. Thus, oxyphenbutazone appears to inhibit the interferon antiviral cascade at a site distinct from prostaglandin biosynthesis. Moreover, the failure to inhibit natural killer cell activation or cellular antigrowth effects of human interferon suggests a pathway different from that associated with the antiviral effect of human interferon.
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PMID:Pleiotropic activities of human interferons are mediated by multiple response pathways. 632 Jan 63

Indomethacin, a potent nonsteroidal inhibitor of prostaglandin synthetase (cyclooxygenase) reduced yields of infectious vesicular stomatitis virus in HEp-2 cells more than 99% if added to cultures at levels of 10(-3)M either before or after infection. Other permissive cell lines differed according to the treatment period and drug level required for restricting productive infections. The inhibitory effect of indomethacin was progressively reduced if infection of cells was delayed for increasing times after drug removal. Strong inhibition of viral replication also occurred in cells treated with the cyclooxygenase antagonists naproxen, phenylbutazone, and oxyphenylbutazone whereas phenacetin, which does not block cyclooxygenase function, was inactive. Enhanced viral replication occurred in indomethacin-treated HEp-2 cultures when these cells were subsequently exposed to such substances as prostaglandin E1, cyclic AMP, or insulin. Conversely, indomethacin-treated cells remained restrictive for VSV if they were subsequently exposed to metabolic inhibitors of functional DNA (actinomycin D or mitomycin C), messenger RNA synthesis (alpha-amanitin), or protein synthesis (cycloheximide) at concentrations that normally do not compromise viral replication. Pretreatment of HEp-2 cells with mitomycin C markedly shifted the dose response for indomethacin-mediated inhibition of VSV from a 90% inhibitory dose of about 10(-4)M to one of 10(-9)M or lower. These findings suggest that preexisting host factors essential for replication of VSV, although rendered nonfunctional by the drug indomethacin, can be replenished unless their synthesis is blocked by various classes of metabolic inhibitors.
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PMID:Reversible restriction of vesicular stomatitis virus in permissive cells treated with inhibitors of prostaglandin biosynthesis. 633 Sep 77