Tumor necrosis factor-alpha is induced through phorbol ester- and glycatedhuman albumin-dependent pathway in THP-1 cells

Tumor necrosis factor-alpha (TNF-alpha) is involved in insulin resistance. Since the fact that peroxisome proliferator-activated receptor gamma (PPAR gamma) ligands inhibit the induction of TNF-alpha by phorbol ester, but not by lipopolysaccharide (LPS), suggests two pathways to induce TNF-alpha, we investigated the mechanisms of glycated human albumin (GHA)- or phorbol es ter-induced TNF-alpha in THP-1 cells. GHA induced TNF-alpha release in diff erentiated THP-1 cells, while phorbol ester induced TNF-alpha release in un differentiated cells but did not induce TNF-alpha in differentiated cells. Forskolin (adenylate cyclase activator) affected more the GHA-induced TNF-a lpha release than the phorbol 12-myristate 13-acetate (PMA)-induced one in undifferentiated cells. Staurosporine [protein kinase-C (PK-C) inhibitor] a nd PD98059 [mitogen-activated protein kinase inhibitor (MAPK)] only partial ly inhibited GHA-induced TNF-alpha. Catalase completely inhibited GHA-induc ed TNF-alpha release; however. superoxide dismutase (SOD) had no effect. Th ese results suggest at least two pathways to induce NTF-alpha (phorbol este r- and GHA-dependent ways) and that GHA-induced TNF-alpha release is throug h predominantly catalase-dependent way in differentiated THP-1 cells. (C) 2 001 Elsevier Science Inc. All rights reserved.