Figure 9.

Proposed model of HA-induced AHR. Oxidative lung injury leads to the release of sHA (15, 17), which forms complexes with IαI HC via TSG-6 (*). HA–HC complexes activate CD44 and TLR4 signaling (15, 18), leading to AHR. High-molecular weight HA and anti-IαI antibodies (15, 17) or genetic absence of IαI (15) or TSG-6 (*) can inhibit the development of AHR. MyD88 (19), RhoA (*), ERK (*), and Akt (*), and calcium influx (17) are intracellular mediators of the sHA-induced AHR. The asterisks in parentheses denote novel contributions of the present paper to the proposed model.