The prototype ligand of theTNFsuperfamily, TNF-α/TNFSF1A, is a pleiotropic cytokine that plays a central role in inflammation and apoptosis (1-4).TNF-α is produced by activated macrophages and other cell types including T and B cells, NK cells, LAK cells, astrocytes, endothelial cells, smooth muscle cells and some tumor cells (5-8).

Rat TNF-α cDNA encodes a 235 amino acid (aa) residue type II membrane protein (9). The 156 aa residue soluble TNF-αis released from the C-terminus of the membrane-anchored TNF-α by TNF-α-converting enzyme (TACE), a matrix metalloprotease (10).

The membrane-anchored form of TNF-α has been shown to have lytic activity and may also have an important role in intercellular communication (11). The biologically active TNF-α has been shown to exist as a trimer (12, 13).TNF-α is reported to promote inflammatory cell infiltration by upregulating leukocyte adhesion molecules on endothelial cells, serve as a chemotactic agent for monocytes, and activate phagocyte killing mechanisms (14). Deficiencies in either TNF-α or its receptors can increase susceptibility to infection by intracellular pathogens (15-16). TNF-α may also play a role in lymphoid tissue development. Knockout mice lack splenic B cell follicles and the ability to form germinal centers (17, 18). Other potential physiological roles for TNF-α and its receptors include regulating the differentiation of hematopoietic stem and progenitor cells (19-21).