Method of screening a compound for its ability to enhance the ability of tristetraprolin to inhibit tumor necrosis factor
AssigneeDuke University
InventorPerry J. Blackshear
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Abstract
The present invention relates, in general, to tristetraprolin (TTP) and, in particular, to methods of modulating levels of tumor necrosis factor α (TNFα) using TTP or nucleic acid sequences encoding same. The invention further relates to methods of screening for compounds for their ability to inhibit TNFα biosynthesis.
Claims7
A method of screening a compound for its ability to enhance the ability of tristetraprolin (TTP) to inhibit tumor necrosis factor (TNFα ) production comprising
- i) contacting said compound with a sample comprising a TNFα encoding sequence, in the presence of TTP or TNFα production-inhibitory polypeptide fragment thereof, under conditions such that said TNFα encoding sequence can be expressed, and
- ii) determining the level of expression of said TNFα encoding sequence and comparing that level to a level of expression obtained in the absence of said compound.
A method of screening a compound for its ability to enhance a TNFα transcription-repressor effect of TTP comprising
- i) contacting said compound with a sample comprising a TNFα promoter sequence operably linked to an encoding sequence, in the presence of TTP or TNFα production-inhibitory polypeptide fragment thereof, under conditions such that said encoding sequence can be expressed, and
- ii) comparing the level of expression of said encoding sequence obtained to a level of expression obtained in the absence of said compound.
A method of screening a compound for its ability to enhance a TNFα mRNA translation-inhibitory effect of TTP comprising
- i) contacting said compound with a sample comprising TNFα mRNA, in the presence of TTP or a TNFα translation-inhibitory fragment thereof, under conditions such that translation of said TNFα mRNA can be effected, and
- ii) determining the level of translation of said TNFα mRNA and comparing that level of translation of said TNFα mRNA to a level of translation of TNFα mRNA obtained in the absence of said compound.
A method of screening a compound for its ability to enhance the ability of TTP to inhibit TNFα processing comprising
- i) contacting the compound with a sample comprising TNFα and TTP or TNFα processing-inhibitory polypeptide fragment thereof, and
- ii) determining the level of processed TNFα in said sample and comparing that level to a level obtained in the absence of said compound.
A method of screening a compound for its ability to enhance the ability of TTP to inhibit TNFα secretion from a cell comprising
- i) contacting a cell comprising TNFα and TTP or a TNFα secretion-inhibitory polypeptide fragment thereof, with said compound, and
- ii) determining the amount of TNFα secreted from said cell and comparing that amount to an amount obtained in the absence of said compound.
Dependencies are inferred from the claim text.