Method to regulate CD40 signaling
AssigneeNational Jewish Medical and Research Center
InventorsErwin W. Gelfand, Gary L. Johnson
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Abstract
The present invention relates to methods useful for identifying compounds capable of specifically controlling CD40 regulation of JNK or p38 activity useful for inhibiting immunoglobulin heavy chain class switching, cytokine production and activation of cells involved in an inflammatory response. The present invention also includes kits to perform such assays and methods to control disease related to such responses.
Claims34
A method to identify a compound that controls CD40 regulation of JNK activity in a cell, comprising:
- (a) contacting a cell with a putative regulatory compound, wherein the cell includes a CD40 protein and a Jun kinase protein;
- and
- (b) assessing the ability of said putative regulatory compound to regulate the activity of said Jun kinase.
A method to identify a compound that controls CD40 regulation of p38 activity in a cell, comprising:
- (a) contacting a cell with a putative regulatory compound, wherein the cell includes CD40 protein and p38 protein;
- and
- (b) assessing the ability of said putative regulatory compound to regulate the activity of said p38 protein.
A regulatory compound identified by said compound's ability to regulate a biological function selected from the group consisting of immunoglobulin heavy chain class switching, cytokine production and inflammatory cell activation, said compound being capable of penetrating the plasma membrane of a cell and of inhibiting the ability of CD40 protein to regulate JNK protein activity in said cell.
A regulatory compound capable of penetrating the plasma membrane of a cell and of inhibiting the ability of CD40 protein to regulate p38 protein activity in said cell, said compound able to regulate a biological function selected from the group consisting of immunoglobulin heavy chain class switching, cytokine production and inflammatory cell activation.
A method to inhibit immunoglobulin heavy chain class switching, comprising inhibiting the activity of a protein selected from the group consisting of Jun kinase protein and p38 protein.
A method to inhibit cytokine production by a cell having CD40, comprising inhibiting the activity of a protein selected from the group consisting of Jun kinase protein and p38 protein.
A method to treat an animal with a disease selected from the group consisting of a disease involving an allergic response and a disease involving an autoimmune disease, said method comprising administering to an animal an effective amount of a therapeutic composition comprising a compound that controls CD40 regulation of the activity of a protein selected from the group consisting of Jun kinase and p38 protein.
A kit to identify compounds that controls CD40 regulation of JNK activity in a cell, said kit comprising:
- (a) a cell comprising a CD40 protein and a Jun kinase protein;
- and
- (b) a means for detecting regulation of said Jun kinase protein.
The kit of claim 32, wherein said cell is selected from the group consisting of Pre-B cells, B lymphocytes, cancer cells, fibroblasts, Langerhans cells, epithelial cells monocytes and dendritic cells.
A kit to identify compounds that controls CD40 regulation of p38 activity in a cell, said kit comprising:
- (a) a cell comprising CD40 protein and p38 protein;
- and
- (b) a means for detecting regulation of said p38 protein.
Dependencies are inferred from the claim text.