METHODS OF TREATING INFLAMMATION
The present invention relates to methods of decreasing inflammation by inhibiting polo-like kinase (Plk)
1 . A method of treating inflammation comprising administering to a subject in need thereof a polo-like kinase (Plk) inhibitor.
2 . The method of claim 1 , wherein the inflammation is associated with an innate immune response to a pathogen or pathogen derived molecule, and wherein the pathogen is a virus.
3 . The method of claim 2 , wherein the pathogen binds to
a) a toll-like receptor on the surface or in endomes of a dendritic cell or
b) a cytosolic RIG-1 like receptor of a dentritic cell.
4 . (canceled)
5 . The method of claim 5 , wherein the inflammation is a symptom of a disease selected from the group consisting of viral infection, bacterial infection, autoimmune disease, or mucositis.
6 . A method of decreasing anti-viral cytokine expression by a dendritic cell comprising contacting the cell with a polo-like kinase (Plk) inhibitor.
7 . The method of claim 6 , wherein the dendritic is in a subject in need of decreased anti-viral cytokine expression.
8 . The method of claim 6 , wherein the cytokine is interferon-β or CXCL-10.
9 . The method of claim 1 , wherein the inhibitor is specific for at least two Plks.
10 . The method of claim 1 , wherein the inhibitor is a pan-specific Plk inhibitor.
11 . The method of claim 9 , wherein the inhibitor is specific for at least Plk2 and Plk4.
12 . The method of claim 10 , wherein the inhibitor is BI 2536, poloxipan, or GW43682X.
13 . A method of identifying genes or genetic elements associated with a pathogen specific response comprising:
a) contacting a dendritic cell with a toll-like receptor agonist; and
b) identify a gene or genetic element whose expression is modulated by step (a).
14 . The method of claim 13 , further comprising
c) perturbing expression of the gene or genetic element identified in step (b) in a dendritic cell that has been contacted with a toll-like receptor agonist.
d) identify a gene whose expression is modulated by step (c).
15 . The method of claim 13 wherein the toll-like receptor agonist is Pam3CSK4, lipopolysaccharide, polyinosinic:polycytidylic acid, gardiquimod, or CpG.
16 . The of claim 13 , wherein the pathogen is a virus, a bacteria, a fungus or a parasite.