Chylomicron remnants upregulate CD40 expression via the ERK pathway and a redox-sensitive mechanism in THP-1 cells
| Autor: | Hiroshi Takaishi, Yoshio Fujioka, Mitsuhiro Yokoyama, Akihiro Takahashi, Kohei Kamemura, Takahiro Taniguchi, Yuichi Ishikawa |
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| Rok vydání: | 2006 |
| Předmět: |
Male
Vasculitis MAPK/ERK pathway MAP Kinase Signaling System Mitogen-Activated Protein Kinase 3 p38 mitogen-activated protein kinases Chylomicron Remnants p38 Mitogen-Activated Protein Kinases Monocytes Cell Line Rats Sprague-Dawley Chylomicron remnant Animals Humans CD40 Antigens Protein kinase A Mitogen-Activated Protein Kinase 1 biology Kinase digestive oral and skin physiology Atherosclerosis Rats Up-Regulation Cell biology Gene Expression Regulation Biochemistry Mitogen-activated protein kinase biology.protein lipids (amino acids peptides and proteins) Reactive Oxygen Species Cardiology and Cardiovascular Medicine Oxidation-Reduction Chylomicron |
| Zdroj: | Atherosclerosis. 187:257-264 |
| ISSN: | 0021-9150 |
| Popis: | CD40 is a 48kDa phosphorylated transmembrane glycoprotein that belongs to the tumor necrosis factor receptor superfamily and may play a role in formation of atherosclerotic plaques. Here, we investigated the effect of chylomicron remnants on CD40 expression in the human premonocytic cell line, THP-1 cells. Chylomicron remnants upregulated the expression of CD40 protein and mRNA in a dose- and time-dependent manner. Further, chylomicron remnants increased the generation of reactive oxygen species as determined by an increasing level of 2',7'-dichlorofluorescein. Pretreatment with the antioxidant, N-acetylcysteine, inhibited chylomicron remnant-induced CD40 protein expression by 60%. On the other hand, chylomicron remnants transiently increased the phosphorylation of extracellular signal-regulated kinase (ERK 1/2) and p38 mitogen-activated protein kinase (MAPK). Pretreatment with the MAPK kinase inhibitor, U0126, completely inhibited chylomicron remnants-induced CD40 protein expression, whereas the p38 MAPK inhibitor, SB203580, had no effect. Pretreatment with N-acetylcysteine had no effect on chylomicron remnant-induced ERK 1/2 phosphorylation. These data suggest that CD40 expression stimulated by chylomicron remnants in THP-1 cells is dependent on ERK 1/2-mediated pathway, which is followed by redox-sensitive mechanism-dependent and independent pathway. Thus, chylomicron remnants may contribute to the formation of atherosclerotic plaques via their immunological and proinflammatory effects. |
| Databáze: | OpenAIRE |
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