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Updated: Oct 7, 2026

Generation of Orthotopic Pancreatic Tumors and Ex vivo Characterization of Tumor-Infiltrating T Cell Cytotoxicity
Published on: December 7, 2019
Tumor necrosis factor-alpha is induced through phorbol ester--and glycated human albumin-dependent pathway in THP-1
T Naitoh1, M Kitahara, N Tsuruzoe
1Nissan Chemical Industries, Ltd., Shiraoka Research Station of Biological Science, 1470 Shiraoka, Minamisaitama, 349-0294, Saitama, Japan. naitouta@nissanchem.co.jp
Abstract:
Tumor necrosis factor-alpha (TNF-alpha) is involved in insulin resistance. Since the fact that peroxisome proliferator-activated receptor gamma (PPARgamma) 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 ester-induced TNF-alpha in THP-1 cells. GHA induced TNF-alpha release in differentiated THP-1 cells, while phorbol ester induced TNF-alpha release in undifferentiated cells but did not induce TNF-alpha in differentiated cells. Forskolin (adenylate cyclase activator) affected more the GHA-induced TNF-alpha release than the phorbol 12-myristate 13-acetate (PMA)-induced one in undifferentiated cells. Staurosporine [protein kinase-C (PK-C) inhibitor] and PD98059 [mitogen-activated protein kinase inhibitor (MAPK)] only partially inhibited GHA-induced TNF-alpha. Catalase completely inhibited GHA-induced TNF-alpha release; however, superoxide dismutase (SOD) had no effect. These results suggest at least two pathways to induce TNF-alpha (phorbol ester- and GHA-dependent ways) and that GHA-induced TNF-alpha release is through predominantly catalase-dependent way in differentiated THP-1 cells.
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