Short-form human MD-2 as a negative regulator of toll-like receptor 4 signaling
The present invention is based on a novel, alternatively spliced human isoform of MD-2 (MD-2s). In addition, the present invention relates to modified MD-2 proteins, wherein one or more tyrosine residues have been mutated to phenylalanine. In various embodiments, the invention relates to methods and kits for preventing, reducing the likelihood of developing and/or treating various conditions using MD-2s. The invention also describes methods of determining the risk of a subject to various conditions.
1. A method of inhibiting lipopolysaccharide (“LPS”) induced lung inflammation in a subject in need thereof, comprising:
providing a purified polypeptide comprising an amino acid sequence that is at least 85% identical to SEQ ID NO:1 or SEQ ID NO:2; and
administering the polypeptide to the subject to inhibit LPS induced lung inflammation.
2. The method of claim 1 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO:1.
3. The method of claim 1 , wherein the polypeptide is glycosylated.
4. The method of claim 1 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO:2.
5. The method of claim 1 , wherein the purified polypeptide comprising an amino acid sequence that is at least 90% identical to SEQ ID NO:1 or SEQ ID NO:2.
6. The method of claim 1 , wherein the purified polypeptide comprising an amino acid sequence that is at least 95% identical to SEQ ID NO:1 or SEQ ID NO:2.
7. The method of claim 1 , wherein the purified polypeptide comprising an amino acid sequence that is at least 99% identical to SEQ ID NO:1 or SEQ ID NO:2.
8. A method of treating asthma, allergic asthma, house dust mite (HDM)-induced allergic airway inflammation, perennial rhinitis, or atopic dermatitis (AD) in a subject in need thereof, comprising:
providing a purified polypeptide comprising an amino acid sequence that is at least 85% identical to SEQ ID NO:1 or SEQ ID NO:2; and
administering the polypeptide to the subject to treat asthma, allergic asthma, house dust mite (HDM)-induced allergic airway inflammation, perennial rhinitis, or atopic dermatitis (AD).
9. The method of claim 8 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO:1.
10. The method of claim 8 , wherein the polypeptide is glycosylated.
11. The method of claim 8 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO:2.
12. The method of claim 8 , wherein the purified polypeptide comprising an amino acid sequence that is at least 90% identical to SEQ ID NO:1 or SEQ ID NO:2.
13. The method of claim 8 , wherein the purified polypeptide comprising an amino acid sequence that is at least 95% identical to SEQ ID NO:1 or SEQ ID NO:2.
14. The method of claim 8 , wherein the purified polypeptide comprising an amino acid sequence that is at least 99% identical to SEQ ID NO:1 or SEQ ID NO:2.