Substrate Stiffness Regulates Proinflammatory Mediator Production through XXXX Activity in Macrophages.

@entity9135 @entity558 @entity4100 @entity2975 @entity2939 @entity2693
UNASSIGNED: Clinical data show that disease adversely affects tissue elasticity or @entity2693 . While macrophage activity plays a critical role in driving disease pathology, there are limited data available on the effects of tissue @entity2693 on macrophage activity. In this study, the effects of substrate @entity2693 on inflammatory mediator production by macrophages were investigated. Bone marrow-derived macrophages were grown on @entity2975 gels that mimicked the @entity2693 of a variety of soft biological tissues. Overall, macrophages grown on soft substrates produced less proinflammatory mediators than macrophages grown on stiff substrates when the endotoxin @entity558 was added to media. In addition, the pathways involved in @entity2693 -regulated proinflammation were investigated. The @entity2939 signaling pathway was examined by evaluating @entity2939 , p-NF-kB @entity9135 , @entity4100 , and p-IkBa expression as well as p-NF-kB @entity9135 translocation. Expression and translocation of the various signaling molecules were higher in macrophages grown on stiff substrates than on soft substrates. Furthermore, @entity2939 knockout experiments showed that @entity2939 activity enhanced proinflammation on stiff substrates. In conclusion, these results suggest that proinflammatory mediator production initiated by @entity2939 is mechanically regulated in macrophages.
