The role of CD44 in the regulation of LPS-TLR signaling in macrophages has recently been reported (94) . CD44 is a transmembrane adhesion molecule and hemopoietic CD44 has an essential role in hyaluronan clearance and resolution of noninfectious lung injury. Following intratracheal LPS treatment, CD44 -/mice demonstrated an exaggerated inflammatory response characterized by increased inflammatory cell recruitment, elevated chemokine expression in bronchoalveolar lavage fluid and a marked increase in NF-κB DNA-binding activity in lung tissue in vivo and in macrophages in vitro. Furthermore, CD44 -/mice were more susceptible to LPS-induced shock. The study further found that the induction of the negative regulators of TLR signaling IL-1R-associated kinase-M, Toll-interacting protein and A20 by intratracheal LPS in vivo and in macrophages in vitro was significantly reduced in CD44 -/mice. Collectively, these data suggest that CD44 plays a role in preventing exaggerated inflammatory responses to LPS by promoting the expression of negative regulators of TLR-4 signaling (94).