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 reducing or inhibiting inflammation associated with brain injury in a patient suffering from a brain injury comprising administering proteoglycan 4 (PRG4) comprising the amino acid sequence of residues 25-1404 of SEQ ID NO:1 to said patient, thereby reducing or inhibiting inflammation in the brain associated with the brain injury to treat the brain injury.
2. The method of claim 1 , wherein the PRG4 is administered to the patient by systemic administration.
3. The method of claim 2 , wherein the administration is intravenous, intraperitoneal, by inhalation, intramuscular, subcutaneous, oral, rectal, buccal, or sublingual.
4. The method of claim 1 , wherein the PRG4 is administered locally to the brain of the patient.
5. The method of claim 4 , wherein the PRG4 is administered to the brain topically or by injection to the patient's brain during surgery.
6. The method of claim 1 , wherein the PRG4 is exogenous human PRG4.
7. The method of claim 1 , wherein the PRG4 is recombinant human PRG4.
8. The method of claim 1 , wherein the PRG4 is administered in an amount insufficient to provide boundary lubrication in the patient.
9. The method of claim 1 , 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.
10. The method of claim 1 , wherein the PRG4 is administered in an amount ranging from 0.1 μg/kg-4000 μg/kg.
11. The method of claim 1 , wherein the brain injury is traumatic brain injury.
12. The method of claim 1 , wherein the brain injury is caused by stroke or embolism.
13. The method of claim 1 , wherein the 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.
14. The method of claim 13 , wherein the cell of (a) and (c) is a brain cell.
15. The method of claim 1 , wherein the administration of the PRG4 relieves pressure in the brain.