Calcium-sensing receptor promotes inflammation through TRPC6 channels/Ca<sup>2+</sup> signaling in macrophages

Xiongying CHEN; Cheng LU; Hui DONG; Feng XU

doi:10.16016/j.2097-0927.202111059

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Calcium-sensing receptor promotes inflammation through TRPC6 channels/Ca²⁺ signaling in macrophages

Basic Medicine | 更新时间：2026-02-13

- Calcium-sensing receptor promotes inflammation through TRPC6 channels/Ca²⁺ signaling in macrophages
- Journal of Army Medical University Vol. 44, Issue 7, Pages: 648-655(2022)
- 作者机构：
  
  1.400014 重庆，重庆医科大学附属儿童医院重症医学科，国家儿童健康与疾病临床医学研究中心，儿童发育疾病研究教育部重点实验室，儿童发育重大疾病国家国际科技合作基地，儿科学重庆市重点实验室
  2.400037 重庆，陆军军医大学(第三军医大学)第二附属医院消化内科
- 作者简介：
- 基金信息：
- DOI：10.16016/j.2097-0927.202111059
  CLC： R329.24;R364.5;R392.12
- Received：08 November 2021，
  
  Revised：2022-01-20，
  
  Published：15 April 2022
- 稿件说明：
移动端阅览
Xiongying CHEN, Cheng LU, Hui DONG, et al. Calcium-sensing receptor promotes inflammation through TRPC6 channels/Ca²⁺ signaling in macrophages[J]. Journal of Army Medical University, 2022, 44(7): 648-655.
DOI：

Xiongying CHEN, Cheng LU, Hui DONG, et al. Calcium-sensing receptor promotes inflammation through TRPC6 channels/Ca²⁺ signaling in macrophages[J]. Journal of Army Medical University, 2022, 44(7): 648-655. DOI： 10.16016/j.2097-0927.202111059.

摘要

目的

观察钙敏感受体(calcium-sensing receptor，CaSR)对RAW264.7细胞炎症反应的影响，并探讨其分子机制。

方法

采用Fura-2荧光探针对RAW264.7细胞质中Ca

进行荧光染色，使用单细胞荧光钙离子检测仪检测CaSR对巨噬细胞内Ca

信号的影响；采用脂多糖(lipopolysaccharide

LPS)诱导细胞炎症模型；采用q-PCR检测IL-1β和IL-18 mRNA表达；ELISA检测IL-1β蛋白含量。

结果

CaSR激动剂CaCl

显著增加RAW264.7胞内钙荧光强度，而CaSR拮抗剂Calhex231可抑制此作用。CaCl

及cinacalcet(CaSR特异性激动剂)都能引起胞内Ca

信号增加，此作用可被Calhex231及瞬时受体电位阳离子通道蛋白6(transient receptor potential cation channel 6，TRPC6)抑制剂SAR7334所抑制(

0.05)。q-PCR检测结果显示：LPS组IL-1β和IL-18 mRNA表达显著高于对照组，cinacalcet进一步增加其表达，而Calhex231及SAR7334可显著抑制此作用(

0.05)。ELISA结果显示：与LPS比较，cinacalcet增加IL-1β蛋白分泌(

0.05)，而此作用可被Calhex231及SAR7334抑制(

0.05)。

结论

在巨噬细胞中，激活CaSR通过TRPC6引起胞内Ca

浓度增加，进而促进IL-1β及IL-18的分泌，最

终促进了可能的炎症反应。

Abstract

Objective

To determine the effect of calcium-sensing receptor (CaSR) on inflammation in RAW264.7 cells and elucidate the underlying molecular mechanisms.

Methods

After Fura-2 fluorescent probe was used to dye intracellular calcium

measurement of intracellular calcium ion concentrations in single living cells were performed using quantitative fluorescence microscopy to detect the effect of CaSR on intracellular calcium signals in RAW264.7 cells. Then after RAW264.7 cells were induced by lipopolysaccharide (LPS) to establish an inflammation model

the mRNA levels of the inflammatory factors interleukin-1β (IL-1β) and interleukin-18 (IL-18) were measured with real-time quantitative PCR (q-PCR). Enzyme-linked immunosorbent assay (ELISA) was adopted to detect the protein contents of IL-1β.

Results

CaSR agonist CaCl

significantly enhanced the calcium fluorescence intensity in RAW264.7 cells

and this promotion effect was inhibited by CaSR antagonist Calhex231. Calcium measurement showed that CaCl

and cinacalcet (CaSR specific agonist) can stimulate RAW264.7 cells and peritoneal macrophages (PMs) to produce Ca

signals

which can be inhibited by Calhex231 and transient receptor potential cation channel 6 (TRPC6) blocker SAR7334

respectively (

0.05). The results of q-PCR indicated that the stimulation of LPS led to significantly higher mRNA levels of IL-1β and IL-18 when compared with of the control group. Cinacalcet treatment further enhanced the mRNA expression of IL-1β and IL-18

while Calhex231 and SAR7334 could significantly inhibit the expression (

0.05). ELISA results showed that compared with the LPS group

cinacalcet induced an increase in IL-1β protein expression (

0.05)

which can be inhibited by Calhex231 and SAR7334 (

0.05).

Conclusion

CaSR activation in macrophages increases intracellular calcium signaling through TRPC6 channels

thus induces IL-1β and IL-18 secretions

and finally promotes inflammation.

关键词

Keywords

references

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⁰

Calcium-sensing receptor promotes inflammation through TRPC6 channels/Ca2+ signaling in macrophages

DOI：10.16016/j.2097-0927.202111059

摘要

Abstract

关键词

Keywords

references

Calcium-sensing receptor promotes inflammation through TRPC6 channels/Ca²⁺ signaling in macrophages