Cytokine Reducing Effect of Azelnidipine in Human Peripheral Blood Mononuclear Cells

Miura, Rika; Nakamura, Kazufumi; Miura, Daiji; Miura, Aya; Kajiya, Masahito; Hisamatsu, Ken-ichi; Nagase, Satoshi; Morita, Hiroshi; Kusano, Kengo; Matsubara, Hiromi; Ohe, Tohru; Ito, Hiroshi

doi:10.1248/bpb.33.1148

Cited by 4 publications

(5 citation statements)

References 45 publications

(65 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Numerous studies have shown that cytosolic calcium ions are involved in the activation of NF-kB. [38][39][40] NF-kB is an essential transcriptional factor that regulates the expression of genes responsible for inammation. In unstimulated cells, NF-kB is inactive and located in the cytoplasm.…”

Section: Resultsmentioning

confidence: 99%

Hydrolyzed tilapia fish collagen modulates the biological behavior of macrophages under inflammatory conditions

Liu

Yang

et al. 2015

RSC Adv.

View full text Add to dashboard Cite

show abstract

Section: Resultsmentioning

confidence: 99%

Hydrolyzed tilapia fish collagen modulates the biological behavior of macrophages under inflammatory conditions

Liu

Yang

et al. 2015

RSC Adv.

View full text Add to dashboard Cite

show abstract

“…The research about the immune-regulatory role of azelnidipine is limited and controversial. On the one hand, azelnidipine was reported to inhibit the differentiation and activation of THP-1 macrophages and the cytokine secretion of peripheral blood mononuclear cells [ 52 , 53 ]. It has also been reported that azelnidipine can enhance the secretion of IL-12 p40 mediated by immune complex, without facilitating the differentiation of Th17 cells, which induces autoimmunity or impair anti-tumor immunity [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

Repositioning Azelnidipine as a Dual Inhibitor Targeting CD47/SIRPα and TIGIT/PVR Pathways for Cancer Immuno-Therapy

et al. 2021

View full text Add to dashboard Cite

Strategies boosting both innate and adaptive immunity have great application prospects in cancer immunotherapy. Antibodies dual blocking the innate checkpoint CD47 and adaptive checkpoint PD-L1 or TIGIT could achieve durable anti-tumor effects. However, a small molecule dual blockade of CD47/SIRPα and TIGIT/PVR pathways has not been investigated. Here, an elevated expression of CD47 and PVR was observed in tumor tissues and cell lines analyzed with the GEO datasets and by flow cytometry, respectively. Compounds approved by the FDA were screened with the software MOE by docking to the potential binding pockets of SIRPα and PVR identified with the corresponding structural analysis. The candidate compounds were screened by blocking and MST binding assays. Azelnidipine was found to dual block CD47/SIRPα and TIGIT/PVR pathways by co-targeting SIRPα and PVR. In vitro, azelnidipine could enhance the macrophage phagocytosis when co-cultured with tumor cells. In vivo, azelnidipine alone or combined with irradiation could significantly inhibit the growth of MC38 tumors. Azelnidipine also significantly inhibits the growth of CT26 tumors, by enhancing the infiltration and function of CD8+ T cell in tumor and systematic immune response in the tumor-draining lymph node and spleen in a CD8+ T cell dependent manner. Our research suggests that the anti-hypertensive drug azelnidipine could be repositioned for cancer immunotherapy.

show abstract

“…Azelnidipine inhibited the death of rat aortic smooth muscle cells in a concentration-dependent manner and also inhibited the activation of c-Jun N-terminal kinase and p38 MAPK [74]. Azelnidipine significantly diminished the phytohemagglutinin-induced increase in intracellular calcium ion concentration and the production of MCP-1 and TNF-a [75]. Azelnidipine decreased the aortic diameter in experimental abdominal aortic aneurysms and reduced the active matrix metalloproteinase (MMP)-2 and MMP-9 levels in the aorta [76].…”

Section: Azelnidipine Treatment In Patients With Essential Hypertensionmentioning

confidence: 93%

Azelnidipine and glucose tolerance: possible indications and treatment selection for hypertensive patients with metabolic disorders

Shimada

Miyauchi

Daida

2014

Expert Review of Cardiovascular Therapy

View full text Add to dashboard Cite

Azelnidipine is a unique dihydropyridine calcium channel blocker with selectivity for L-type calcium channels that has been launched for the treatment of hypertension. Azelnidipine exhibits long-acting blood pressure-lowering effects without increasing heart rate. High blood pressure is associated with many metabolic disorders, including glucose intolerance and insulin resistance. Antihypertensive medications that interfere with various steps in the renin-angiotensin system improve glucose tolerance and insulin resistance; however, the effects of calcium channel blockers on glucose metabolism and insulin resistance remain controversial. Recent studies have demonstrated that azelnidipine could improve insulin resistance and glucose tolerance by potentially inhibiting sympathetic nerve activity. In addition, azelnidipine exhibits anti-inflammatory and anti-oxidative effects, suggesting that it is a beneficial antihypertensive agent with anti-atherogenic and cardioprotective effects for the treatment of not only hypertensive patients with glucose intolerance, but also those with metabolic disorders.

show abstract

Cytokine Reducing Effect of Azelnidipine in Human Peripheral Blood Mononuclear Cells

Cited by 4 publications

References 45 publications

Hydrolyzed tilapia fish collagen modulates the biological behavior of macrophages under inflammatory conditions

Hydrolyzed tilapia fish collagen modulates the biological behavior of macrophages under inflammatory conditions

Repositioning Azelnidipine as a Dual Inhibitor Targeting CD47/SIRPα and TIGIT/PVR Pathways for Cancer Immuno-Therapy

Azelnidipine and glucose tolerance: possible indications and treatment selection for hypertensive patients with metabolic disorders

Contact Info

Product

Resources

About