Hyaluronan Is Not a Ligand but a Regulator of Toll-Like Receptor Signaling in Mesangial Cells: Role of Extracellular Matrix in Innate Immunity

Figure 8

Influence of different concentrations of heparin on specific stimulation of TLR2 and TLR4. Both cell types were coincubated TLR ligands with and without hyaluronidase of constant concentrations. Heparins of different sizes were tested on both cell types coincubated with the TLR ligand and hyaluronidase to demonstrate the inhibitory effect of heparin on IL-6 expression. (a) enoxaparin on pMC/TLR4^−/− (TLR4-deficient cells), (b) heparin on pMC/TLR4^−/−, (c) enoxaparin on pMC/TLR2^−/− (TLR2-deficient cells), and (d) heparin on pMC/TLR2^−/−. PAM: PAM3CysSK4; HYAL: hyaluronidase; ENOX: enoxaparin; HEP: heparin; data are means ± SD, ns: not significant, ^∗𝑃≤0.05--^∗∗∗∗𝑃<0.0001.

(a)

(b)

(c)

(d)