Candesartan inhibits inflammation through an angiotensin II type 1 receptor independent way in human embryonic kidney epithelial cells

Yu, Ying; Jiang, Hua; Niu, Yangyang; Zhang, Xiaoqin; Zhang, Yingying; Liu, X I; Qi, Tao; Chen, Yu

doi:10.1590/0001-3765201920180699

Cited by 10 publications

(9 citation statements)

References 11 publications

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“…However, there was no difference in the normotensive and hypertensive animals' responses, suggesting that its signaling was not related to the bone fragility differences between the Wistar and SHRs. Yu et al (2019) demonstrated the in vitro anti-inflammatory effect of candesartan in human embryonic kidney epithelial cells (HEK lineage), possibly associated with reduced oxidative stress, independent of the At1r receptor. The present study's results suggest that other mechanisms could have been involved in the protective effect of TELM on the bone.…”

Section: Discussionmentioning

confidence: 99%

Telmisartan Prevents Alveolar Bone Loss by Decreasing the Expression of Osteoclasts Markers in Hypertensive Rats With Periodontal Disease

et al. 2020

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Periodontal disease (PD) is a prevalent inflammatory disease with the most severe consequence being the loss of the alveolar bone and teeth. We therefore aimed to evaluate the effects of telmisartan (TELM), an angiotensin II type 1 receptor (Agtr1) antagonist, on the PD-induced alveolar bone loss, in Wistar (W) and Spontaneous Hypertensive Rats (SHRs). PD was induced by ligating the lower first molars with silk, and 10 mg/kg TELM was concomitantly administered for 15 days. The hemimandibles were subjected to microtomography, ELISA was used for detecting tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), CXCL3, and CCL2, while qRT-PCR was used for analyzing expression of components of renin-angiotensin system (RAS) (Agt, Ace, Agt1r, Agt2r, Ace2, and Masr), and bone markers (Runx2, Osx, Catnb, Alp, Col1a1, Opn, Ocn, Bsp, Bmp2, Trap, Rank, Rankl, CtsK, Mmp-2, Mmp-9, and osteoclast-associated receptor (Oscar)). The SHR + PD group showed greater alveolar bone loss than the W + PD group, what was significantly inhibited by treatment with TELM, especially in the SHR group. Additionally, TELM reduced the production of TNF-α, IL-1β, and CXCL3 in the SHR group. The expression of Agt increased in the groups with PD, while Agtr2 reduced, and TELM reduced the expression of Agtr1 and increased the expression of Agtr2, in W and SHRs. PD did not induce major changes in the expression of bone formation markers, except for the expression of Alp, which decreased in the PD groups. The bone resorption markers expression, Mmp9, Ctsk, and Vtn, was higher in the SHR + PD group, compared to the respective control and W + PD group. However, TELM attenuated these changes and increased the expression of Runx2 and Alp. Our study suggested that TELM has a protective effect on the progression of PD, especially in hypertensive animals, as evaluated by the resorption of the lower alveolar bone. This can be partly explained by the modulation in the expression of Angiotensin II receptors (AT1R and AT2R), reduced production of inflammatory mediators, the reduced expression of resorption markers, and the increased expression of the bone formation markers.

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Section: Discussionmentioning

confidence: 99%

Telmisartan Prevents Alveolar Bone Loss by Decreasing the Expression of Osteoclasts Markers in Hypertensive Rats With Periodontal Disease

et al. 2020

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“…CS has been demonstrated to exert anti-inflammatory activities in vitro and in vivo . CS significantly reduced the expression levels of IL-6 and transforming growth factor-β (TGF-β) in TNF-α-stimulated human embryonic kidney epithelial cells ( 41 ). CS decreased the expression of Th1 and Th2 cytokines in the lung tissues of mice with ovalbumin-induced allergic asthma ( 42 ).…”

Section: Discussionmentioning

confidence: 99%

Repositioning of the Angiotensin II Receptor Antagonist Candesartan as an Anti-Inflammatory Agent With NLRP3 Inflammasome Inhibitory Activity

Lin

Hsiao

et al. 2022

Front. Immunol.

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Aberrant activation of the NLRP3 inflammasome promotes the pathogenesis of many inflammatory diseases. The development of the NLRP3 inflammasome inhibitors from existing drugs for new therapeutic purposes is becoming more important. Candesartan is an angiotensin II receptor antagonist widely used as a blood pressure-lowering drug; however, the inhibitory potential of candesartan on the NLRP3 inflammasome has not yet been investigated. We demonstrated that candesartan significantly inhibited the NLRP3 inflammasome and pyroptosis in macrophages. Mechanistic analysis revealed that candesartan inhibited the expression of NLRP3 and proIL-1β by suppressing NF-κB activation and reducing the phosphorylation of ERK1/2 and JNK1/2. Candesartan reduced mitochondrial damage and inhibited the NLRP3 inflammasome assembly by suppressing NLRP3 binding to PKR, NEK7 and ASC. In addition, candesartan inhibited IL-1β secretion partially through autophagy induction. Furthermore, oral administration of candesartan reduced peritoneal neutrophil influx, NLRP3 and ASC expression in peritoneal cells, and lavage fluid concentrations of active caspase-1, IL-1β, IL-6 and MCP-1 in uric acid crystal-injected mice. These results indicated that candesartan has board anti-inflammatory effects and has the potential to be repositioned to ameliorate inflammatory diseases or NLRP3-associated complications.

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“…Furthermore, candesartan inhibits inflammation by modulating signaling cascades dependent on TNF-α, IL-1beta, IL-2, IL-6, TGF-β, and NF-κB. In addition, it reduces the formation of ROIs by phagocytes and lowers the expression of CD25 and IL-2 release by T cells [113,[124][125][126][127][128][129]. However, this medicament seems to not affect the secretion of IL-10 [130], similarly to olmesartan [121].…”

Section: Candesartan Irbesartanmentioning

confidence: 99%

“…-IL-1beta [31], IL-6 and IL-8 concentration [31,32,85]; -CRP concentration [41]; -TNF-alfa concentration [41,113,[124][125][126][127][128][129]; -lymphocyte proliferation and IFN-gamma production in vitro assays, and suppressed antigen-specific Th1 and Th2 lymphocytes in vivo [115]; -formation of ROIs by phagocytes [113,[124][125][126][127][128][129]; -the expression of CD25 and IL-2 release by T cells [113,[124][125][126][127][128][129]; -the general number of immune cells in bronchoalveolar lavage fluid [125]; -the release of Th2-lymphocyte (IL-4, IL-5 and IL-13) and Th1-lymphocyte (IL-2 and IFN-γ) cytokines [125].…”

Section: Reduction Inmentioning

confidence: 99%

Immunomodulatory Activity of the Most Commonly Used Antihypertensive Drugs—Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers

Bryniarski

Nazimek

Marcinkiewicz

2022

IJMS

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This review article is focused on antihypertensive drugs, namely angiotensin converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB), and their immunomodulatory properties reported in hypertensive patients as well as in experimental settings involving studies on animal models and cell lines. The immune regulatory action of ACEI and ARB is mainly connected with the inhibition of proinflammatory cytokine secretion, diminished expression of adhesion molecules, and normalization of CRP concentration in the blood plasma. The topic has significant importance in future medical practice in the therapy of patients with comorbidities with underlying chronic inflammatory responses. Thus, this additional effect of immune regulatory action of ACEI and ARB may also benefit the treatment of patients with metabolic syndrome, allergies, or autoimmune disorders.

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Candesartan inhibits inflammation through an angiotensin II type 1 receptor independent way in human embryonic kidney epithelial cells

Cited by 10 publications

References 11 publications

Telmisartan Prevents Alveolar Bone Loss by Decreasing the Expression of Osteoclasts Markers in Hypertensive Rats With Periodontal Disease

Telmisartan Prevents Alveolar Bone Loss by Decreasing the Expression of Osteoclasts Markers in Hypertensive Rats With Periodontal Disease

Repositioning of the Angiotensin II Receptor Antagonist Candesartan as an Anti-Inflammatory Agent With NLRP3 Inflammasome Inhibitory Activity

Immunomodulatory Activity of the Most Commonly Used Antihypertensive Drugs—Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers

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