Gene interactions and pathways from curated databases and text-mining
J Immunol 2002, PMID: 12218154

Suppression of monocyte chemoattractant protein 1, but not IL-8, by alprazolam: effect of alprazolam on c-Rel/p65 and c-Rel/p50 binding to the monocyte chemoattractant protein 1 promoter region.

Oda, Taiko; Ueda, Atsuhisa; Shimizu, Noriaki; Handa, Hiroshi; Kasahara, Tadashi

Alprazolam is a hypnotic/tranquilizer that has been shown to specifically inhibit the platelet-activating factor (PAF)-induced aggregation of human platelets. The goal of this study was to elucidate whether alprazolam modulates IL-1alpha-initiated responses. For this purpose we investigated the effects of alprazolam on the IL-1alpha-induced production of inflammatory cytokines (IL-8 and monocyte chemoattractant protein 1 (MCP-1)) in a human glioblastoma cell line, T98G, and explored the signaling pathways involved. We found that alprazolam inhibited IL-1alpha-elicited MCP-1 production within a range of 0.1-3 micro M. In contrast, it did not inhibit IL-1alpha-induced IL-8 production. Although NF-kappaB is involved in regulating the IL-1alpha-induced expression of MCP-1 and IL-8, the degradation of IkappaB-alpha stimulated by IL-1alpha was not inhibited by alprazolam. Alprazolam prevented NF-kappaB from binding to the MCP-1 promoter region (the A2 and A1 oligonucleotide probes), but binding of NF-kappaB to IL-8/NF-kappaB was not inhibited. Moreover, alprazolam inhibited c-Rel/p50 binding to the A2 oligonucleotide probe, but not p50/p65 from binding to the IL-8/NF-kappaB site. While AP-1 is involved in regulating the IL-1alpha-induced expression of IL-8, but not MCP-1, alprazolam potentiated the binding of c-Jun/c-Fos to the AP-1 oligonucleotide probe. These results show that the inhibition of IL-1alpha-mediated MCP-1 production by alprazolam is mainly due to inhibition of c-Rel/p65 and c-Rel/p50 binding to the MCP-1 promoter region, since alprazolam did not affect the IL-1alpha-mediated activation of NF-kappaB (p50/p65) or AP-1 (c-Jun/c-Fos) binding to the IL-8 promoter region. In conclusion, a new action of alprazolam was elucidated, as shown in the inhibition of c-Rel/p65- and c-Rel/p50-regulated transcription.

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Text Mining Data

monocyte chemoattractant protein 1 → IL-1alpha: " For this purpose we investigated the effects of alprazolam on the IL-1alpha induced production of inflammatory cytokines ( IL-8 and monocyte chemoattractant protein 1 ( MCP-1 ) ) in a human glioblastoma cell line, T98G, and explored the signaling pathways involved "

IL-8 → IL-1alpha: " For this purpose we investigated the effects of alprazolam on the IL-1alpha induced production of inflammatory cytokines ( IL-8 and monocyte chemoattractant protein 1 ( MCP-1 ) ) in a human glioblastoma cell line, T98G, and explored the signaling pathways involved "

IL-8 → IL-1alpha: " In contrast, it did not inhibit IL-1alpha induced IL-8 production "

MCP-1 → IL-1alpha: " Although NF-kappaB is involved in regulating the IL-1alpha induced expression of MCP-1 and IL-8, the degradation of IkappaB-alpha stimulated by IL-1alpha was not inhibited by alprazolam "

IL-8 → IL-1alpha: " Although NF-kappaB is involved in regulating the IL-1alpha induced expression of MCP-1 and IL-8 , the degradation of IkappaB-alpha stimulated by IL-1alpha was not inhibited by alprazolam "

MCP-1 — NF-kappaB: " Although NF-kappaB is involved in regulating the IL-1alpha induced expression of MCP-1 and IL-8, the degradation of IkappaB-alpha stimulated by IL-1alpha was not inhibited by alprazolam "

IL-8 — NF-kappaB: " Although NF-kappaB is involved in regulating the IL-1alpha induced expression of MCP-1 and IL-8 , the degradation of IkappaB-alpha stimulated by IL-1alpha was not inhibited by alprazolam "

IL-8/NF-kappaB ⊣ NF-kappaB: " Alprazolam prevented NF-kappaB from binding to the MCP-1 promoter region ( the A2 and A1 oligonucleotide probes ), but binding of NF-kappaB to IL-8/NF-kappaB was not inhibited "

MCP-1 → IL-1alpha: " While AP-1 is involved in regulating the IL-1alpha induced expression of IL-8, but not MCP-1 , alprazolam potentiated the binding of c-Jun/c-Fos to the AP-1 oligonucleotide probe "

IL-8 → IL-1alpha: " While AP-1 is involved in regulating the IL-1alpha induced expression of IL-8 , but not MCP-1, alprazolam potentiated the binding of c-Jun/c-Fos to the AP-1 oligonucleotide probe "

MCP-1 — AP-1: " While AP-1 is involved in regulating the IL-1alpha induced expression of IL-8, but not MCP-1 , alprazolam potentiated the binding of c-Jun/c-Fos to the AP-1 oligonucleotide probe "

IL-8 — AP-1: " While AP-1 is involved in regulating the IL-1alpha induced expression of IL-8 , but not MCP-1, alprazolam potentiated the binding of c-Jun/c-Fos to the AP-1 oligonucleotide probe "

MCP-1 ⊣ c-Rel/p50: " These results show that the inhibition of IL-1alpha mediated MCP-1 production by alprazolam is mainly due to inhibition of c-Rel/p65 and c-Rel/p50 binding to the MCP-1 promoter region, since alprazolam did not affect the IL-1alpha mediated activation of NF-kappaB ( p50/p65 ) or AP-1 ( c-Jun/c-Fos ) binding to the IL-8 promoter region "

MCP-1 → c-Rel/p65: " These results show that the inhibition of IL-1alpha mediated MCP-1 production by alprazolam is mainly due to inhibition of c-Rel/p65 and c-Rel/p50 binding to the MCP-1 promoter region, since alprazolam did not affect the IL-1alpha mediated activation of NF-kappaB ( p50/p65 ) or AP-1 ( c-Jun/c-Fos ) binding to the IL-8 promoter region "

MCP-1 → IL-1alpha: " These results show that the inhibition of IL-1alpha mediated MCP-1 production by alprazolam is mainly due to inhibition of c-Rel/p65 and c-Rel/p50 binding to the MCP-1 promoter region, since alprazolam did not affect the IL-1alpha mediated activation of NF-kappaB ( p50/p65 ) or AP-1 ( c-Jun/c-Fos ) binding to the IL-8 promoter region "

AP-1 → IL-1alpha: " These results show that the inhibition of IL-1alpha mediated MCP-1 production by alprazolam is mainly due to inhibition of c-Rel/p65 and c-Rel/p50 binding to the MCP-1 promoter region, since alprazolam did not affect the IL-1alpha mediated activation of NF-kappaB ( p50/p65 ) or AP-1 ( c-Jun/c-Fos ) binding to the IL-8 promoter region "

NF-kappaB → IL-1alpha: " These results show that the inhibition of IL-1alpha mediated MCP-1 production by alprazolam is mainly due to inhibition of c-Rel/p65 and c-Rel/p50 binding to the MCP-1 promoter region, since alprazolam did not affect the IL-1alpha mediated activation of NF-kappaB ( p50/p65 ) or AP-1 ( c-Jun/c-Fos ) binding to the IL-8 promoter region "

Manually curated Databases

No curated data.