Suppression of Fas/APO-1-Mediated Apoptosis by Mitogen-Activated Kinase Signaling

• DOI: 10.4049/jimmunol.160.6.2626
• Publication Date: 2022-12-31T14:17:51Z
• Authors: Tim H. Holmström; Sek C. Chow; Iina Elo; Eleanor T. Coffey; Sten Orrenius; Lea Sistonen; John E. Eriksson
• Keywords: Jurkat cells; Fas ligand

Abstract Jurkat T cells undergo rapid apoptosis upon stimulation of the Fas/APO-1 (CD95) receptor. We examined role mitogen-activated protein kinase (MAPK) cascade as a negative regulator Fas-mediated apoptosis. To this end, we used both physiologic and artificial activators MAPK, all which activate MAPK by distinct routes. activity could be efficiently elevated two cell mitogens, lectin PHA an agonistic Ab to receptor complex well type 1 2A phosphatase inhibitor, calyculin A, C-activating phorbol ester, tetradecanoyl acetate. All these treatments were effective in preventing characteristic early late features apoptosis, including activation caspases. Our results indicate that activities intervene upstream caspase activation. The degree different stimuli our study corresponds their potency inhibit indicating serves efficient modulator modulation was further corroborated transient transfection with constitutively active kinase, resulting complete inhibition Fas response, whereas dominant form had no effect. Furthermore, inhibitory effect abolished specific inhibitor PD 098059. Modulation responses signaling may determine persistence immune response explain insensitivity recently activated stimulation.