Use of PRG4 as an anti-inflammatory agent
Disclosed herein are methods of using PRG4 glycoprotein, also known as lubricin, to reduce, inhibit, or down-regulate pro-inflammatory pathways in patients at risk of or suffering from an inflammatory response or allergy symptom through CD44 antagonization, regulating pro-inflammatory cytokine production, inhibiting NF-κB translocation and/or facilitating removal of inflammation-inducing cellular or matrix debris or allergens.
1. A method of treating an inflammatory bowel disease in a patient suffering from the inflammatory bowel disease, comprising administering proteoglycan 4 (PRG4) comprising the amino acid sequence of residues 25-1404 of SEQ ID NO:1 to the gastrointestinal tract of the patient in need thereof by oral administration, rectal administration, administration to the colon, administration to the small intestine, administration to the stomach, or through a combination thereof.
2. The method of claim 1 , wherein the PRG4 is recombinant exogenous human PRG4.
3. The method of claim 1 , wherein PRG4 is administered in an amount insufficient to provide boundary lubrication in the patient.
4. The method of claim 1 , wherein PRG4 is administered in an amount ranging from 0.1 μg/kg-4000 μg/kg.
5. The method of claim 1 , wherein said PRG4
a) binds a CD44 receptor on a cell in said patient;
b) reduces or inhibits the production of a pro-inflammatory cytokine in said patient; and/or
c) reduces or inhibits the translocation of NF-κB in a cell in said patient, thereby reducing or inhibiting the inflammatory response in said patient.
6. The method of claim 5 , wherein the cell is a gastric cell, intestinal cell, or colon cell.
7. The method of claim 5 , wherein the pro-inflammatory cytokine is selected from the group consisting of IL-6, IL-8, TNF-α, CCL11, and GRO.
8. The method of claim 1 , wherein the inflammatory bowel disease is Crohn's disease or ulcerative colitis.
9. The method of claim 1 , wherein the PRG4 is administered orally.
10. The method of claim 9 , wherein the PRG4 is administered orally into the gastrointestinal tract of the patient as a tablet, a capsule, as a solution by ingestion, or by feeding tube.
11. The method of claim 10 , wherein the tablet or capsule comprises a substance that degrades when exposed to conditions present in the gastrointestinal tract.
12. The method of claim 1 , wherein the PRG4 is administered rectally.
13. The method of claim 12 , wherein the PRG4 is administered by enema.
14. The method of claim 13 , wherein the PRG4 is administered in an amount of 100 mL to 4 L in a concentration ranging from 10 μg/mL to 200 μg/mL.
15. The method of claim 1 , wherein the PRG4 is administered to the bowel via a colostomy.
16. The method of claim 1 , wherein the PRG4 is administered to the small intestine or large intestine by J-tube.
17. The method of claim 1 , wherein administration of a laxative followed by fasting precedes administering the PRG4.
18. The method of claim 1 , wherein the PRG4 is administered by injection directly to the stomach, colon, small-intestine, or rectum.
19. The method of claim 1 , wherein PRG4 is administered locally to provide a coating of PRG4 from a PRG4 solution.