TLR4 and Sepsis: In Porphyromonas gingivalis LPS-induced sepsis in mice, TLR4 caused cardiac dysfunction by activating NADPH oxidase-4, increasing ROS, stimulating calmodulin-dependent protein kinase-II with phosphophorylation of RyR2 and of phospholamban, a negative regulator of SR Ca2+ uptake [204].