Calcium-sensing receptor in the T lymphocyte enhanced the apoptosis and cytokine secretion in sepsis

Wu, Chunli; Wu, Qiuyue; Du, Jingjing; Zeng, Jingya; Li, Tingting; Xu, Chi; Sun, Yihua

doi:10.1016/j.molimm.2014.08.007

Cited by 32 publications

(27 citation statements)

References 24 publications

(24 reference statements)

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“…In this sense, inhibition of CaSR activity in the WAT of obese patients may represent a novel therapeutic approach in this obesity epidemic era. The effects here described are in accordance with recent findings indicating that CaSR activation participates in many inflammatory processes, such as recognition of necrotic cells (Rossol et al, 2012) and pathologies like asthma (Yarova et al, 2015), myocardial infarction (Liu et al, 2015), and sepsis (Wu et al, 2015). On the other hand, CaSR-induced inflammation in the gastrointestinal tract has been proposed to be a conditioning agent for the appropriate function of the intestinal epithelial barrier (Owen et al, 2016).…”

Section: Resultssupporting

confidence: 91%

Calcium Sensing Receptor as a Novel Mediator of Adipose Tissue Dysfunction: Mechanisms and Potential Clinical Implications

Bravo-Sagua¹,

Mattar

Díaz

et al. 2016

Front. Physiol.

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Obesity is currently a serious worldwide public health problem, reaching pandemic levels. For decades, dietary and behavioral approaches have failed to prevent this disease from expanding, and health authorities are challenged by the elevated prevalence of co-morbid conditions. Understanding how obesity-associated diseases develop from a basic science approach is recognized as an urgent task to face this growing problem. White adipose tissue (WAT) is an active endocrine organ, with a crucial influence on whole-body homeostasis. WAT dysfunction plays a key role linking obesity with its associated diseases such as type 2 diabetes mellitus, cardiovascular disease, and some cancers. Among the regulators of WAT physiology, the calcium-sensing receptor (CaSR) has arisen as a potential mediator of WAT dysfunction. Expression of the receptor has been described in human preadipocytes, adipocytes, and the human adipose cell lines LS14 and SW872. The evidence suggests that CaSR activation in the visceral (i.e., unhealthy) WAT is associated with an increased proliferation of adipose progenitor cells and elevated adipocyte differentiation. In addition, exposure of adipose cells to CaSR activators in vitro elevates proinflammatory cytokine expression and secretion. An increased proinflammatory environment in WAT plays a key role in the development of WAT dysfunction that leads to peripheral organ fat deposition and insulin resistance, among other consequences. We propose that CaSR may be one relevant therapeutic target in the struggle to confront the health consequences of the current worldwide obesity pandemic.

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Section: Resultssupporting

confidence: 91%

Calcium Sensing Receptor as a Novel Mediator of Adipose Tissue Dysfunction: Mechanisms and Potential Clinical Implications

Bravo-Sagua¹,

Mattar

Díaz

et al. 2016

Front. Physiol.

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“…Intriguingly, supplementing these diabetic pregnant rats with a diet rich in unsaturated fat 15 days prior to pregnancy and throughout gestation prevented this enhanced response to ionomycin. As calcium mobilization and calcium-sensing receptor (CaSR)-induced secretion of cytokines like TNF-α is increased in T cells from inflammatory disease such as sepsis [ 155 ], we propose that these pathways link obesity and inflammation to the development of PE.…”

Section: Effects Of Obesity On Placental Ischemia-induced Periphermentioning

confidence: 99%

Immune Mechanisms Linking Obesity and Preeclampsia

2015

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Preeclampsia (PE) is characterized by hypertension occurring after the twentieth week of pregnancy. It is a significant contributor to maternal and perinatal morbidity and mortality in developing countries and its pervasiveness is increasing within developed countries including the USA. However, the mechanisms mediating the pathogenesis of this maternal disorder and its rising prevalence are far from clear. A major theory with strong experimental evidence is that placental ischemia, resulting from inappropriate remodeling and widening of the maternal spiral arteries, stimulates the release of soluble factors from the ischemic placenta causing maternal endothelial dysfunction and hypertension. Aberrant maternal immune responses and inflammation have been implicated in each of these stages in the cascade leading to PE. Regarding the increased prevalence of this disease, it is becoming increasingly evident from epidemiological data that obesity, which is a state of chronic inflammation in itself, increases the risk for PE. Although the specific mechanisms whereby obesity increases the rate of PE are unclear, there are strong candidates including activated macrophages and natural killer cells within the uterus and placenta and activation in the periphery of T helper cells producing cytokines including TNF-α, IL-6 and IL-17 and the anti-angiogenic factor sFlt-1 and B cells producing the agonistic autoantibodies to the angiotensin type 1 receptor (AT1-aa). This review will focus on the immune mechanisms that have been implicated in the pathogenesis of hypertension in PE with an emphasis on the potential importance of inflammatory factors in the increased risk of developing PE in obese pregnancies.

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“…In addition, Li et al found that the activation of CaSR in normal human peripheral blood T lymphocytes could promote the secretions of IL-6 and TNF-α through MAPK and NF-κB pathways [ 11 ]. Wu et al also indicated that CaSR in rat sepsis peripheral blood T lymphocytes influence lymphocytes to release cytokines and lymphocyte apoptosis [ 12 , 13 ]. However, there is no evidence to make certain the role of CaSR in human T lymphocytes on AMI occurrence and development.…”

Section: Introductionmentioning

confidence: 99%

Calcium-Sensing Receptor in Human Peripheral Blood T Lymphocytes Is Involved in the AMI Onset and Progression through the NF-κB Signaling Pathway

Zeng

Pan

et al. 2016

IJMS

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Acute myocardial infarction (AMI) is a condition triggered by an inflammatory process that seriously affects human health. Calcium-sensing receptor (CaSR) in T lymphocytes is involved during the inflammation reaction. However, the relationship between them is not very clear. In this study, we collected human peripheral blood T lymphocytes from patients with AMI and in different stages of percutaneous coronary intervention (PCI) (at the onset of AMI, the first day after PCI (PCI-1), PCI-3, and PCI-5) to study the CaSR and NF-κB pathway protein expression, cytokine release and T cell apoptosis. The results showed that the expressions of CaSR, P-p65, Caspase-12, and the secretions of Th-1 and Th-2 type cytokines were increased at the onset of AMI, especially on the PCI-1. Meanwhile, the apoptosis rate of CD3+, CD4+ and CD8+ T lymphocytes also increased. However, from PCI-3, all the indicators began to decline. In addition, we also found that positive CaSR small interfering RNA (siRNA) transfection in T lymphocytes and NF-κB pathway blocker Bay-11-7082 reversed the increased expressions of CaSR, P-p65, Caspase-12, reduced the secretions of Th-1 and Th-2 type cytokines, and decreased T lymphocytes apoptosis rate not only in the AMI patients but also in the normal controls. All of these results indicated that CaSR in the human peripheral blood T lymphocytes were involved in the AMI onset and progression, which probably was related to the NF-κB pathway. Our study demonstrated the relationship between AMI and CaSR, and will provide new effective prevention theory and new targets for drug treatment.

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Calcium-sensing receptor in the T lymphocyte enhanced the apoptosis and cytokine secretion in sepsis

Cited by 32 publications

References 24 publications

Calcium Sensing Receptor as a Novel Mediator of Adipose Tissue Dysfunction: Mechanisms and Potential Clinical Implications

Calcium Sensing Receptor as a Novel Mediator of Adipose Tissue Dysfunction: Mechanisms and Potential Clinical Implications

Immune Mechanisms Linking Obesity and Preeclampsia

Calcium-Sensing Receptor in Human Peripheral Blood T Lymphocytes Is Involved in the AMI Onset and Progression through the NF-κB Signaling Pathway

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