Association of Advanced Glycation End Products with A549 Cells, a Human Pulmonary Epithelial Cell Line, Is Mediated by a Receptor Distinct from the Scavenger Receptor Family and RAGE

Nakano, Nahoko; Fukuhara-Takaki, Kaori; Jono, Tadashi; Nakajou, Keisuke; Eto, Nobuaki; Horiuchi, Seikoh; Takeya, Motohiro; Nagai, Ryoji

doi:10.1093/jb/mvj092

Cited by 22 publications

(20 citation statements)

References 39 publications

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“…The observed RAGE-banding patterns from these colonic cells were virtually identical with that detected from lung epithelial cell A549 (Fig. 1), in which RAGE expression has been reported previously (38). Expression of RAGE in another colonic epithelial cell, Caco2, was also detected in the experiments (data not shown) (39).…”

Section: Rage Is Expressed In Human Intestinal Epitheliumsupporting

confidence: 87%

“…Due to the critical role of RAGE in regulating diabetes-associated chronic inflammations, most research on RAGE has been focused on diabetes-related organs and cells. Although several studies have reported RAGE expression in some epithelial cells, including eye epithelial cells (55,56), lung epithelial cells (38), and skin cells (57), so far there is no direct evidence of RAGE in the intestinal epithelium, in particular under inflammatory conditions. In this study, we demonstrated that RAGE is expressed in both cultured human intestinal epithelial cells and normal and inflammatory intestinal tissues.…”

Section: Discussionmentioning

confidence: 99%

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Receptor for Advanced Glycation Endproducts Mediates Neutrophil Migration across Intestinal Epithelium

Zen

Chen

et al. 2007

The Journal of Immunology

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Receptor for advanced glycation endproducts (RAGE) is an Ig superfamily cell surface receptor that interacts with a diverse array of ligands associated with inflammatory responses. In this study, we provide evidence demonstrating that RAGE is involved in inflammatory responses in the intestines. We showed that RAGE is expressed in intestinal epithelial cells, primarily concentrated at the lateral membranes close to the apical cell junction complexes. Although RAGE expression was low in epithelium under normal conditions, this protein was up-regulated after treatment with the inflammatory cytokines IFN-γ and/or TNF-α. RAGE expression was also elevated in colon tissue samples from patients with inflammatory bowel diseases. Using in vitro transmigration assays, we found that RAGE mediates neutrophil (polymorphonuclear leukocytes (PMN)) adhesion to, and subsequent migration across, intestinal epithelial monolayers. This activity appears to be mediated by the binding of RAGE to the PMN-specific β2 integrin CD11b/CD18. Thus, these results provide a novel mechanism for the regulation of PMN transepithelial migration and may suggest a new therapeutic target for intestinal inflammation.

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Section: Rage Is Expressed In Human Intestinal Epitheliumsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Receptor for Advanced Glycation Endproducts Mediates Neutrophil Migration across Intestinal Epithelium

Zen

Chen

et al. 2007

The Journal of Immunology

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“…As shown in Fig. 9B, Western blot analysis showed that RAGE is highly expressed on A549 cells, a human pulmonary epithelial cell line, as reported previously (Nakano et al, 2006). We confirmed that AGE-2 and AGE-3 at 100 g/ml Fig.…”

Section: Involvement Of Ifn-␥ and Tnf-␣ In The Effectsupporting

confidence: 90%

Advanced Glycation End Products Subspecies-Selectively Induce Adhesion Molecule Expression and Cytokine Production in Human Peripheral Blood Mononuclear Cells

Takahashi

Mori

Wake³

et al. 2009

J Pharmacol Exp Ther

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Advanced glycation end products (AGEs) are proteins or lipids that become glycated after exposure to diverse reducing sugars. Accumulation of AGEs induces diabetes complications. Microinflammation is a common major mechanism in the pathogenesis of diabetic vascular complications. Activation of monocytes/macrophages and T cells plays roles in the pathogenesis of atherosclerosis. The activation of T cells requires the enhanced expression of adhesion molecules on monocytes. AGEs activate monocytes by engaging the receptor for AGE (RAGE); however, little is known about the profile of agonist activity of diverse AGE moieties on monocytes. We investigated the effect of four distinct AGE subtypes (AGE-modified bovine serum albumin; AGE-2, AGE-3, AGE-4, and AGE-5) at concentrations ranging from 0.1 to 100 g/ml on the expression of intercellular adhesion molecule-1, B7.1, B7.2, and CD40 on monocytes and its impact on the production of interferon-␥ and tumor necrosis factor-␣ in human peripheral blood mononuclear cells. Among the AGEs examined, AGE-2 and AGE-3 selectively induced adhesion molecule expression and cytokine production. Antagonism experiments using antibodies against adhesion molecules demonstrated that cell-to-cell interaction between monocytes and T/natural killer cells was involved in AGE-2-and AGE-3-induced cytokine production. AGE-2 and AGE-3 up-regulated the expression of RAGE on monocytes. The effects of AGE-2 and AGE-3 were inhibited by nuclear factor-B and p38 mitogen-activated protein kinase inhibitors. These results indicated that AGE-2 and AGE-3 activated monocytes via RAGE, leading to the up-regulation of adhesion molecule expression and cytokine production.

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“…However, the 13 C NMR spectrum (in CDCl 3 at 22 or 40 1C) of 1 showed 24 resolved peaks, which lacked one carbon atom. During the process of investigation, we found that a methylene signal of C-22 was not observed in the above 13 C NMR spectra. On the other hand, the signals of H-22 and C-22 were clearly visible when the NMR data were acquired in pyridine-d 5 at -35 1C (see Table 2).…”

Section: Isolation Procedures For Nbri17671 (1)mentioning

confidence: 94%

“…The organic layer was dried over Na 2 SO 4 and concentrated to dryness. The resulting residue was purified by HPLC (column: Inertsil ODS, GL Sciences, Tokyo, Japan; 20 mmÂ250 mm, eluent: 60-100% CH 3 Compound 2 was obtained as a complex mixture of tautomers, 11 and the 1 H and 13 C NMR signals depicted above are those of the predominant enol form as shown in Figure 2. A new antitumor compound, NBRI17671 M Kawada et al…”

Section: Synthesismentioning

confidence: 99%

NBRI17671, a new antitumor compound, produced by Acremonium sp. CR17671

et al. 2010

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The interaction between the receptor for advanced glycation end-product (RAGE) and amphoterin has an important role in tumor growth and metastasis. Because the abrogation of the interaction results in the inhibition of the tumor growth and metastasis, we designed a screening system for an inhibitor of the interaction between RAGE and amphoterin. In the course of our screening of the inhibitor, we isolated a novel natural compound NBRI17671 (1) from the fermentation broth of Acremonium sp. CR17671. We also modified 1 into a more active NBRI17671al (2). Although 1 at 50 lg ml -1 weakly inhibited binding of various cells to amphoterin, 2 at 50 lg ml -1 inhibited it by >50% of control. Compound 2 effectively inhibited the tumor growth of glioma and lung tumor xenografts in mice at 25 mg kg -1 . Furthermore, 2 was found to downregulate mitogen-activated protein kinase (MAPK) activity in the tumor cells. Keywords: amphoterin; antitumor drug; natural compound; RAGE; tumor growth INTRODUCTIONThe receptor for advanced glycation end-products (RAGE) 1 is a multiligand cell surface receptor and has a critical role in various diseases such as diabetes, 2 Alzheimer's disease 3 and tumor. 4 It is reported that soluble RAGE suppresses accelerated diabetic atherosclerosis by interfering the association between advanced glycation end-products and RAGE in the cells of blood vessels. 5 Because the abrogation of the association between RAGE and a respective ligand is an attractive therapeutic target, we have especially focused on tumor therapy. Amphoterin, also known as HMGB1, is one of the ligands of RAGE,6 and is expressed at high levels in various kinds of cancers. 7 RAGE expression is not restricted to tumor cells, as cells in blood vessels also express RAGE. Thus, the interaction between RAGE and amphoterin involves not only tumor growth and motility directly, but also tumor angiogenesis. 8 Indeed, several papers reported that blockade of RAGE-amphoterin interaction suppresses tumor growth and metastasis using soluble RAGE, truncated amphoterin or antisense. 4,9,10 We therefore hypothesized that a small molecule inhibitor of the interaction between RAGE and amphoterin will become a new antitumor drug. We then designed the screening system and searched for the inhibitor. As a result, we have found a novel natural compound from a fungal strain Acremonium sp. CR17671. In this study we describe the isolation, structure determination and biological activity of NBRI17671 (1) and the synthesis and biological activity of a more active derivative of 1, (2).

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Association of Advanced Glycation End Products with A549 Cells, a Human Pulmonary Epithelial Cell Line, Is Mediated by a Receptor Distinct from the Scavenger Receptor Family and RAGE

Cited by 22 publications

References 39 publications

Receptor for Advanced Glycation Endproducts Mediates Neutrophil Migration across Intestinal Epithelium

Receptor for Advanced Glycation Endproducts Mediates Neutrophil Migration across Intestinal Epithelium

Advanced Glycation End Products Subspecies-Selectively Induce Adhesion Molecule Expression and Cytokine Production in Human Peripheral Blood Mononuclear Cells

NBRI17671, a new antitumor compound, produced by Acremonium sp. CR17671

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