Up-regulation of the proteasome subunit LMP7 in tissues of endotoxemic rats

The proteasome has been implicated in systemic responses to infection or in flammatory stimuli including catabolism of skeletal muscle. Cytokines Inclu ding tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamm a) are known to be elevated systemically and locally under these conditions . They are also known to be potent inducers of three peptide subunits of th e proteasome, including LMP7, that replace constitutively expressed subunit s and change enzymatic properties. To determine whether endotoxemia alters the expression of inducible proteasome subunits, we examined the levels of LMP7 in tissues from rats 3 days after the injection of lipopolysaccharide (LPS) or normal saline solution (NS). By bath immunoblotting and immunohist ochemistry, significant increases in levels of LMP7 were observed in the he art, kidney, and lung of animals given LPS as compared with results in NS-t reated animals, whereas immunoblotting revealed no changes in LMP7 levels i n skeletal muscle or brain. Increased expression of LMP7 was limited to cer tain subpopulations of cells and was further localized at the subcellular l evel. Decreases in organ weight were also documented for organs in which th e expression of LMP7 was up-regulated Systemic or local release of cytokine s or other proinflammatory mediators is suggested as the most likely mechan ism for changes in LMP7 expression during endotoxemia, Changes in LMP7 expr ession may have functional consequences that contribute to organ dysfunctio n during systemic responses to infection and inflammatory stimuli.