Expression of Costimulatory Molecules (4-1BBL and Fas) and Major Histocompatibility Class I Chain-Related A (MICA) in Aortic Tissue with Takayasu’s Arteritis

Seko, Yoshinori; Sugishita, Kazuyuki; Satō, Osamu; Takagi, Akio; Tada, Yusuke; Matsuo, Hiroshi; Yagita, Hideo; Okumura, Ko; Nagai, Ryozo

doi:10.1159/000076437

Cited by 59 publications

(41 citation statements)

References 17 publications

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“…In addition, the expression of 4-1BB is not restricted to immune cells; its expression has been demonstrated on blood vessel endothelial cells, smooth muscle cells, neurons, astrocytes, and microglia (Boussaud et al, 1998;Broll et al, 2001;Reali et al, 2003;Seko et al, 2004). When T cells are activated by a variety of stimuli such as anti-CD3 mAb, concanavalin A (Con A), phytohaemagglutinin (PHA), interleukin (IL)-2, IL-4, anti-CD28 mAb, phorbol myristyl acetate (P), or ionomycin (I), 4-1BB is stably upregulated (Garni-Wagner et al, 1996;Kim et al, 2003;Pollok et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Regulation of Mouse 4-1BB Expression: Multiple Promoter Usages and a Splice Variant

Kim

Kwon

2011

Molecules and Cells

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The expression of 4-1BB has been known to be dependent on T cell activation. Recent studies have, however, revealed that 4-1BB expression is not restricted to T cells. We sought to determine the molecular basis for the differential gene expression. Here we report the expression pattern of two mouse 4-1BB transcripts, type I and type II. Whereas the type I transcript was specifically expressed on immune organ as previously reported, the type II transcript was ubiquitously expressed in tissues and various cell lines. However, both type I and type II transcript were highly induced on activated T cells. Primer extension assay of the two 4-1BB transcripts suggested that mouse 4-1BB had more than two transcripts. Using luciferase assay we have identified three promoter regions (PI, PII and PIII), which located on upstream region of second exon 1, first exon 1, and exon 2, respectively. In particular, the type I transcript was preferentially induced when naïve T cells are stimulated by anti-CD3 monoclonal antibody (mAb) since NF-κB specifically binds to the putative NF-κB element of PI. We have also shown that a splice variant, in which the transmembrane domain was deleted, could inhibit 4-1BB signaling. The splicing variant was highly induced by TCR stimulation. Our results reveal 4-1BB also has a negative regulation system through soluble 4-1BB produced from a splice variant induced under activation conditions.

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Section: Introductionmentioning

confidence: 99%

Regulation of Mouse 4-1BB Expression: Multiple Promoter Usages and a Splice Variant

Kim

Kwon

2011

Molecules and Cells

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“…18 Expression of major histocompatibility complex (MHC)-I, MHC-II and co-stimulatory molecules on the infiltrating cells has also been reported. 19,20 These observations suggest that vascular inflammation driven by antigen-specific immune reactions plays a key role in the pathogenesis of the arterial stenoses in Takayasu arteritis and may also facilitate restenosis after coronary stenting. Sirolimus was originally discovered as an antibiotic and then developed as an immunosuppressive agent.…”

Section: Discussionmentioning

confidence: 98%

Sirolimus-Eluting Stent for In-Stent Restenosis of Left Main Coronary Artery in Takayasu Arteritis

Furukawa

Tamura

Toma

et al. 2005

Circ J

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akayasu arteritis is a form of large vessel vasculitis with an unclear pathogenesis, although autoimmune mechanisms as well as a genetic etiology are possibly involved in its evolution and progression. Because Takayasu arteritis affects the entire aorta and its major branches, it occasionally complicates coronary artery stenoses. Although revascularization therapy is recommended for such patients, obstructive lesions in the subclavian arteries, active inflammation or severe calcification of the aorta often render coronary bypass grafting impossible. In addition, the long-term outcome of percutaneous coronary intervention (PCI) in patients with Takayasu arteritis is largely unknown. We describe a case of Takayasu arteritis with left main coronary artery (LMCA) stenosis that was successfully treated by sirolimus-eluting stent (SES) deployment after repeated in-stent restenosis following bare metal stenting. Case ReportA 53-year-old woman was admitted to hospital because of worsening exertional angina. At the age of 42 years, she had been diagnosed as having Takayasu arteritis. Magnetic resonance angiography and 99m technetium pulmonary perfusion scintigraphy revealed an occlusion of the left pulmonary artery and multiple mild stenoses in both of the common carotid and subclavian arteries. She had been treated with oral glucocorticoids (prednisolone) and was generally in good condition for the past 11 years until she presented with exertional angina. Angiography in August 2003 revealed severe (90%) ostial stenosis in a short LMCA with involvement of the distal bifurcation (Fig 1A), an intact right coronary artery ( Fig 1B) and total occlusion of the left pulmonary artery (Fig 1C). Collateral circulation via the intercostal arteries had developed between the left internal thoracic artery and left pulmonary circulation. Although coronary bypass surgery was recommended as the first therapeutic option, the patient refused open-chest surgery and PCI was then considered as another option. Because the patient developed unstable angina, a bare metal stent (3.0×15 mm ACS RX Multi-Link™, Guidant) was urgently implanted in her LMCA in September 2003; at that time, SES were not available in Japan. The kissing balloon technique was used for stenosis of the bifurcation of the left anterior descending artery (LAD) (4.0×15 mm POWERSAIL, Guidant) and left circumflex artery (LCX) (2.5×20 mm Maverick2, Boston Scientific). The 90% LMCA stenosis was successfully dilated to 0% (Fig 1D) and the angina completely disappeared. The daily dose of oral prednisolone was increased from 12.5 mg to 20 mg because the blood test suggested enhanced activity of the Takayasu arteritis, showing positive C-reactive protein (CRP: 3.6 mg/dl) and an augmented erythrocyte sedimentation rate (48 mm/h). These inflammatory parameters normalized within 1 month. However, 3 months later, the patient was readmitted for recurrence of the angina. She underwent balloon angioplasty using a 4.0×18 mm POWERSAIL (Guidant) for the LMCA and LAD, and 2.5×15 mm Stormer (Medt...

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“…The ligand of CD137 (CD137L) is primarily expressed on antigen‐presenting cells (dendritic cells, monocytes/macrophages, and B cells), human primary T cells22 and cardiac myocytes in myocarditis and aortic tissue in arteritis 23, 24. In addition to mediating costimulation on T‐cell activation and survival, the engagement of CD137L with soluble CD137 can also elicit reverse signaling and, in turn, stimulate the activation, migratory capabilities, and survival of monocytes expressing CD137L 25, 26.…”

Section: Discussionmentioning

confidence: 99%

Increased Soluble CD137 Levels and CD4+ T‐Cell‐Associated Expression of CD137 in Acute Atherothrombotic Stroke

et al. 2018

Clinical Translational Sci

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As a proinflammatory cytokine, CD137 (4‐1BB, TNFRSF9) is present in membrane‐bound and soluble forms. Increased expression of CD137 was recently found in T cells in human atherosclerotic plaques. However, the exact role of CD137 in ischemic stroke is not clear. In this study we analyzed the protein levels of soluble CD137 (sCD137) and the expression of CD137 on CD4+ T cells in the peripheral blood of patients with acute atherothrombotic stroke by using the cytometry beads array (CBA) and flow cytometry. Within 24 hours of onset, the stroke patients showed elevated levels of sCD137 (2.7 pg/ml) and CD137 expression on CD4+ T cells (4.9 ± 3.2%) compared with normal controls (1.1 pg/ml, P < 0.01; 1.3 ± 1.0%, P < 0.01). Alterations in CD137 expression may enhance ischemia‐induced inflammatory responses via bidirectional signaling and, consequently, aggravate brain injury in early stages of this disorder.

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Expression of Costimulatory Molecules (4-1BBL and Fas) and Major Histocompatibility Class I Chain-Related A (MICA) in Aortic Tissue with Takayasu’s Arteritis

Cited by 59 publications

References 17 publications

Regulation of Mouse 4-1BB Expression: Multiple Promoter Usages and a Splice Variant

Regulation of Mouse 4-1BB Expression: Multiple Promoter Usages and a Splice Variant

Sirolimus-Eluting Stent for In-Stent Restenosis of Left Main Coronary Artery in Takayasu Arteritis

Increased Soluble CD137 Levels and CD4+ T‐Cell‐Associated Expression of CD137 in Acute Atherothrombotic Stroke

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