Inhibiting P2Y12 receptor relieves LPS‐induced inflammation and endothelial dysfunction
Abstract Background Acute lung injury (ALI) is characterized by abnormal inflammatory response without effective therapies. P2Y12 receptor (P2Y12R) plays a vital role in inflammatory response. This study intends to explore whether P2Y12R antagonists can inhibit LPS‐induced inflammatory injury of hum...
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| Format: | Article |
| Language: | English |
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Wiley
2022-10-01
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| Series: | Immunity, Inflammation and Disease |
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| Online Access: | https://doi.org/10.1002/iid3.697 |
| _version_ | 1798000241999347712 |
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| author | Xiuxia Han |
| author_facet | Xiuxia Han |
| author_sort | Xiuxia Han |
| collection | DOAJ |
| description | Abstract Background Acute lung injury (ALI) is characterized by abnormal inflammatory response without effective therapies. P2Y12 receptor (P2Y12R) plays a vital role in inflammatory response. This study intends to explore whether P2Y12R antagonists can inhibit LPS‐induced inflammatory injury of human pulmonary microvascular endothelial cells (HPMVECs) and endothelial cell dysfunction. Methods Using a cell model of ALI, the role of P2Y12R was investigated in LPS‐induced HPMVECs. The expression of P2Y12R was detected by RT‐qPCR and Western blot analysis assay and TNF‐α, IL‐1β, and IL‐6 levels were analyzed by RT‐qPCR. NO levels were also analyzed through NO kit. The levels of NF‐κB p65, P‐IκB‐α, and IκB‐α, as well as p‐AKT and eNOS levels were detected by Western blot analysis assay. Wound healing assay was performed to evaluate HPMVECs migration. FITC‐dextran was used to evaluate endothelial cell permeability, and the analysis of adherens junction protein VE‐cadherin and endothelial cell tight junction proteins ZO‐1, Claudin 5 and Occludin expression was performed by RT‐qPCR and Western blot analysis assay. Results In vitro, LPS increased the expression levels of P2Y12R and pro‐inflammatory mediators (TNF‐α, IL‐1β, and IL‐6), followed by a decrease in HPMVECs migration. In addition, LPS led to an increase in endothelial cell permeability. P2Y12R antagonists Ticagrelor or clopidogrel treatment significantly reversed these effects of LPS. Conclusion The inhibitor of P2Y12R was able to decrease inflammatory response, promote migration and improve endothelial cell function and permeability, suggesting a key role of P2Y12R in ALI. |
| first_indexed | 2024-04-11T11:17:21Z |
| format | Article |
| id | doaj.art-432085d1e946497e825454eeac641898 |
| institution | Directory Open Access Journal |
| issn | 2050-4527 |
| language | English |
| last_indexed | 2024-04-11T11:17:21Z |
| publishDate | 2022-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Immunity, Inflammation and Disease |
| spelling | doaj.art-432085d1e946497e825454eeac6418982022-12-22T04:27:11ZengWileyImmunity, Inflammation and Disease2050-45272022-10-011010n/an/a10.1002/iid3.697Inhibiting P2Y12 receptor relieves LPS‐induced inflammation and endothelial dysfunctionXiuxia Han0Medical Department of Shandong University Hospital Jinan Shandong ChinaAbstract Background Acute lung injury (ALI) is characterized by abnormal inflammatory response without effective therapies. P2Y12 receptor (P2Y12R) plays a vital role in inflammatory response. This study intends to explore whether P2Y12R antagonists can inhibit LPS‐induced inflammatory injury of human pulmonary microvascular endothelial cells (HPMVECs) and endothelial cell dysfunction. Methods Using a cell model of ALI, the role of P2Y12R was investigated in LPS‐induced HPMVECs. The expression of P2Y12R was detected by RT‐qPCR and Western blot analysis assay and TNF‐α, IL‐1β, and IL‐6 levels were analyzed by RT‐qPCR. NO levels were also analyzed through NO kit. The levels of NF‐κB p65, P‐IκB‐α, and IκB‐α, as well as p‐AKT and eNOS levels were detected by Western blot analysis assay. Wound healing assay was performed to evaluate HPMVECs migration. FITC‐dextran was used to evaluate endothelial cell permeability, and the analysis of adherens junction protein VE‐cadherin and endothelial cell tight junction proteins ZO‐1, Claudin 5 and Occludin expression was performed by RT‐qPCR and Western blot analysis assay. Results In vitro, LPS increased the expression levels of P2Y12R and pro‐inflammatory mediators (TNF‐α, IL‐1β, and IL‐6), followed by a decrease in HPMVECs migration. In addition, LPS led to an increase in endothelial cell permeability. P2Y12R antagonists Ticagrelor or clopidogrel treatment significantly reversed these effects of LPS. Conclusion The inhibitor of P2Y12R was able to decrease inflammatory response, promote migration and improve endothelial cell function and permeability, suggesting a key role of P2Y12R in ALI.https://doi.org/10.1002/iid3.697clopidogrelinflammationmigrationP2Y12 receptorticagrelor |
| spellingShingle | Xiuxia Han Inhibiting P2Y12 receptor relieves LPS‐induced inflammation and endothelial dysfunction Immunity, Inflammation and Disease clopidogrel inflammation migration P2Y12 receptor ticagrelor |
| title | Inhibiting P2Y12 receptor relieves LPS‐induced inflammation and endothelial dysfunction |
| title_full | Inhibiting P2Y12 receptor relieves LPS‐induced inflammation and endothelial dysfunction |
| title_fullStr | Inhibiting P2Y12 receptor relieves LPS‐induced inflammation and endothelial dysfunction |
| title_full_unstemmed | Inhibiting P2Y12 receptor relieves LPS‐induced inflammation and endothelial dysfunction |
| title_short | Inhibiting P2Y12 receptor relieves LPS‐induced inflammation and endothelial dysfunction |
| title_sort | inhibiting p2y12 receptor relieves lps induced inflammation and endothelial dysfunction |
| topic | clopidogrel inflammation migration P2Y12 receptor ticagrelor |
| url | https://doi.org/10.1002/iid3.697 |
| work_keys_str_mv | AT xiuxiahan inhibitingp2y12receptorrelieveslpsinducedinflammationandendothelialdysfunction |