Compositions and methods for treating allergic inflammatory conditions
Provided are methods for increasing SPINK7 anti-proteinase activity in a target tissue of a subject having an allergic inflammatory condition characterized by inflammation of a squamous epithelium in the target tissue, the method comprising inhibiting kallikrein 5 (KLK5) proteinase activity in the target tissue. Suitable KLK5 inhibitors may include a KLK5-Fc fusion protein, a KLK5 anti-sense polynucleotide, a KLK5-directed miRNA, a KLK5-directed shRNA, a KLK5-directed antibody, or a coumarin compound such as 3-(3-chlorophenyl) carboxy-7-hydroxymethyl coumarin or 3-carboxy-7-hydroxymethyl coumarin.
1. A method for increasing SPINK7 anti-proteinase activity in a target tissue of a human subject having an allergic inflammatory condition characterized by inflammation of a squamous epithelium in the target tissue, the method comprising inhibiting kallikrein 5 (KLK5) proteinase activity in the target tissue.
2. The method of claim 1 , wherein the target tissue is esophageal tissue.
3. The method of claim 2 , wherein the method comprises administering a KLK5 inhibitor to the subject.
4. The method of claim 3 , wherein the KLK5 inhibitor is administered in an amount effective to ameliorate inflammation of a squamous epithelium in the target tissue.
5. The method of claim 4 , wherein the KLK5 inhibitor is selected from the group consisting of a KLK5-Fc fusion protein, a KLK5 anti-sense polynucleotide, a KLK5-directed miRNA, a KLK5-directed shRNA, and a KLK5-directed antibody.
6. The method of claim 4 , wherein the KLK5 inhibitor is 3-(3-chlorophenyl) carboxy-7-hydroxymethyl coumarin or 3-carboxy-7-hydroxymethyl coumarin.
7. The method of claim 4 , wherein the KLK5 inhibitor is alpha-1 antitrypsin (A1AT).
8. The method of claim 4 , wherein the method further comprises administering at least one additional active agent to the subject, and wherein the at least one additional active agent is selected from the group consisting of an anti-inflammatory agent selected from an IL-13 inhibitor, a non-steroidal anti-inflammatory drug (NSAID), a steroid, and a cytokine inhibitor, and a PPI inhibitor, and combinations thereof.
9. The method of claim 1 , wherein the subject is in need of therapy for-esophageal eosinophilia.
10. The method of claim 1 , wherein the subject is in need of therapy for eosinophilic esophagitis.
11. A method for increasing SPINK7 anti-proteinase activity in esophageal tissue of a subject having an allergic inflammatory condition characterized by inflammation of a squamous epithelium in the target tissue, the method comprising administering to the subject a pharmaceutical composition comprising an amount of an inhibitor of kallikrein 5 (KLK5), wherein the amount is sufficient to inhibit kallikrein 5 (KLK5) proteinase activity in the esophageal tissue.
12. The method of claim 11 , wherein the amount is an amount effective to ameliorate inflammation of a squamous epithelium in the esophageal tissue.