TUMOR NECROSIS FACTOR-ALPHA AND INTERLEUKIN-1 INDUCE ACTIVATION OF MAP KINASE AND SAP KINASE IN HUMAN NEUROMA FIBROBLASTS

摘要: Abstract Two cytokines, tumor necrosis factor-alpha (TNF-α) and interleukin-1 (IL-1), which are released by macrophages during the early inflammatory phase of nerve injury, known to induce activation mitogen-activated protein kinase (MAPK) stress-activated (SAPK), locate at different signal transduction pathways involved in cell cycle G 0 / 1 transition cellular proliferation human fibroblasts. Activation these two kinases cytokines may stimulate fibroblast damaged nerves thereby play a role formation neuroma, disorganized mass tissue that interferes with neural regeneration repair. To investigate possibility this mechanism is operative neuroma formation, we used cultured, serum-starved fibroblasts from surgically removed neuromas stimulated TNF-α and/or IL-1α IL-1β, measured MAPK SAPK using myelin basic (MBP) c-Jun (1–169) glutathione S-agarose transferase (GST) fusion as substrates. For comparison, cultures were also phorbol 12-myristate 13-acetate (PMA) platelet-derived growth factor-AB (PDGF-AB), potent activator for MAPK. both forms IL-1 produced rapid MAPK, peak 15 min stimulation, 30 stimulation. combined either or IL-1β synergistic effect on The increases induced similar PMA PDGF-AB. confirm presence immunoprecipitation immunoblotting carried out experimental control lysates. increased SAPK, but lesser extent than PDGF-AB much less effective stimulating SAPK. Our findings indicate activate parallel fibroblasts, they relatively stronger activators Previous studies have convincingly demonstrated proliferation. results our study suggest frustrating functional after injury kinases, which, turn, leads neuromas. © 1997 Elsevier Science Ltd. All rights reserved