kavain and Bacteroidaceae-Infections

TNF-a is an important cytokine mediator of inflammation which suggests that inhibition of TNF activity may provide potential for clinical application. Recent data indicated that treatment of both human and mouse cells with Kavain significantly modulates P. gingivalis- and LPS-induced TNF-α expression. In order to obtain a selective analog with optimized biological activity and structural physico-chemical properties of Kavain, Kavain analogs were designed and synthesized and found one Kavain analogue (named Kav001) that is similar to Kavain but soluble and does not induce a significant toxicity. Both studies in vitro and in vivo treatment by Kav001 showed stronger biological function as compared to Kavain. Furthermore, most mouse bone marrow macrophages up-regulated Bcl-6 while down-regulating LITAF expression after treatment with Kav001 for 36 h. Consequently, this led to an extension of macrophage pseudopods due to its immune response to P.g. infection/LPS stimulation.

Topics: Animals; Anticonvulsants; Arthritis, Experimental; Bacteroidaceae Infections; Cytokines; Inflammation; Lipopolysaccharides; Macrophages, Peritoneal; Male; Mice; Mice, Inbred C57BL; Porphyromonas gingivalis; Pyrones; Tumor Necrosis Factor-alpha