Soluble Heparan Sulfate Fragments Generated by Heparanase Trigger the Release of Pro-Inflammatory Cytokines through TLR-4
Figure 9
Model of cytokine upregulation in response to HPSE.
Schematic model of the proposed function of HPSE in releasing pro-inflammatory cytokines. (1) HPSE cleaves and solubilises HS fragments from the cell surface of immune cells. (2) HS fragments then signal through MyD88-dependent receptors, of which TLR4 is one, and this leads to NF-κB cleavage and activation. (3) NF-κB-dependent upregulation of cytokine production and release, including IL-8, IL-10, IL-6, TNF and IL-1β. (4) Cytokines are involved in inflammatory events including chemoattraction and increased antibody production. (5) These events contribute to the induction of an inflammatory response.