NF-kappa B activation by CD26 antigen is independent of dipeptidyl peptidase IV activity

CD26 antigen distribution among lymphoid and non lymphoid cells is widely documented. This antigen contains dipeptidyl peptidase IV (DPP-IV) enzymatic activity and it is thought to play an important role in the processes of cellular activation. We show that cell activation through the CD26 pathway induces DNA binding of the NF-kappa B/rel family of transcription factors in human peripheral T lymphocytes, in the hepatoma cell line HepG2, and in Hela cells. The functional significance of the NF-kappa B in the CD26 mediated signal transduction pathway is demonstrated by transient transfection analysis, since treatment of HepG2 and Hela cells with the anti-CD26 monoclonal antibodies 134-2C2 and 1F7 resulted in transactivation of a luciferase reported construct driven by three KB sites. The ability of CD26 to activate NF-kappa B seems to be independent of its DPP-IV activity but it is likely that CD26 activation results in an increase of intracellular levels of reactive oxygen intermediates as deduced from the antioxidant pyrrolidine dithiocarbamate blocking of the induction of NF-kappa B activity on CD26 activated cells. These results provide new evidence that the CD26 antigen plays a pivotal role in the mechanisms of activation of CD26 expressing cells.