Fig. 5.

Outside-to-inside signal by adalimumab and infliximab.

This is a novel mechanism for the inhibition of transmembrane TNF-α-bearing cells by anti-TNF antibodies. In the absence of NK cells or complement, adalimumab or infliximab induces G0/G1 cell cycle arrest and apoptosis, which inhibits TNF-α-producing cells and leads to an anti-inflammatory response. A number of molecules (p21^WAF1/CIP1, Bax, Bak and ROS) were involved in these intracellular signalling events through the intracellular domain of transmembrane TNF-α. These signalling molecules are supposed to be associated with p53 activation. Three serine residues in the intracellular domain of transmembrane TNF-α are essential for the activities. Bak and Bax are proapoptotic multidomain molecules; tmTNF: transmembrane TNF-α.