Participation of the proteasome on the TNF-α, IL-1β and IL-6 release by U937 cells

Proteasome between other activities is critically involved in the regulation of transcription factors such as p53 or NF-kB. For activation and nucleus translocation of the NFkB transcription factor, its required the phosphorylation, ubiquinitation and degradation of the IkB in the proteasome, which is a multimeric proteases complex present in the inactive form of the NFkB. Once activated NFkB factor, into the nucleus plays a central role in the expression of powerful proinflammatory mediators such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin 6 (IL-6). In this work the liberation of TNF-alpha, IL-1beta and IL-6 on cultures of U937 cells stimulated with lipopolysaccharide (LPS) + phorbolmyristate (PMA) was studied either in presence or absence of the proteasome inhibitor MG-132. Our results in the U937 cell cultures, show that the proteasome inhibitor MG-132, significantly inhibits the secretion of these proinflammatories cytokines.