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.