A Feed-Forward Loop Involving Hyaluronic Acid and Toll-Like Receptor-4 as a Treatment for Colitis?

DSS induces HA fragments that, via TLR-4, are anti-inflammatory in colitis. DSS administration is a well-utilized model of colitis. Zheng et al now provide complex insights into the effect of DSS in the gut.⁶ They demonstrate that DSS can act via TLR-4 in macrophages to induce HAS leading to the production of HA fragments (blue lines). These fragments in turn, also acting via TLR-4, induce COX-2 leading to PGE₂ production, which has a cytoprotective effect and is anti-inflammatory in the epithelium (red lines). These fragments can also induce further fragment production in a feed-forward effect, propagating the anti-inflammatory response. Administering HA fragments are anti-inflammatory in the DSS model, possibly indicating a new therapeutic approach for colitis.