Intracellular signaling pathways involved in lipopolysaccharide (LPS)-stimulated TNF-alpha release by cultured Kupffer cells

The paradigm of LPS-stimulated TNF-alpha release is important for several c linical problems including TNF-alpha release during reperfusion injury (sho ck, transplantation), sepsis, and alcoholic liver disease. The intracellular signaling pathways for LPS-stimulated TNF-alpha synthesis are not fully known. We postulated that LPS must be endocytosed, acidified in endocytic vesicles and intracellular calcium increased for signaling to induce TNF-alpha synthesis (1). Our Aim was to determine the sequence of intracellular pathways required fo r LPS-stimulated TNF-alpha release.