Glyburide attenuates ozone‐induced pulmonary inflammation and injury by blocking the NLRP3 inflammasome

Abstract

Glyburide is a classic antidiabetic drug that is dominant in inflammation regulation, but its specific role in ozone‐induced lung inflammation and injury remains unclear. In order to investigate whether glyburide prevents ozone‐induced pulmonary inflammation and its mechanism, C57BL/6 mice were intratracheally pre‐instilled with glyburide or the vehicle 1 hour before ozone (1 ppm, 3 hours) or filtered air exposure. After 24 hours, the total inflammatory cells and total protein in bronchoalveolar lavage fluid (BALF) were detected. The pathological alternations in lung tissues were evaluated by HE staining. The expression of NLRP3, interleukin‐1β (IL‐1β), and IL‐18 protein in lung tissues was detected by immunohistochemistry. Western blotting was used to examine the levels of caspase‐1 p10 and active IL‐1β protein. Levels of IL‐1β and IL‐18 in BALF were measured using ELISA kits. Glyburide treatment decreased the total cells in BALF, the inflammatory score, and the mean linear intercept induced by ozone in lung tissues. In addition, glyburide inhibited the expression of NLRP3, IL‐18, and IL‐1β protein in lung tissues, and also suppressed NLRP3 inflammasome activation, including caspase‐1 p10, active IL‐1β protein in lung tissues, IL‐1β, and IL‐18 in BALF. These results demonstrate that glyburide effectively attenuates ozone‐induced pulmonary inflammation and injury via blocking the NLRP3 inflammasome.

Glibenclamide Alleviates LPS-Induced Acute Lung Injury through NLRP3 Inflammasome Signaling Pathway

“…In our study, administration of glibenclamide inhibits LPS-stimulated lung edema, vascular hyperpermeability damage, and inflammatory cell infiltration. These results indicate that in addition to the various models of ALI reported in previous studies [11][12][13][14], glibenclamide also exerts a protective role in the current model of LPS-induced ALI.…”

“…And so far, there have been considerable interventions described in the publications to prevent ALI/ARDS [23][24][25]. Among them, the antiinflammatory property of glibenclamide in ALI/ARDS has been increasingly concerned and validated effectively in various animal models of ALI, including oleic acid-, ozone-, radiation-, hemorrhagic shock-, and ventilator-induced ALI [11][12][13][14]. In our study, administration of glibenclamide inhibits LPS-stimulated lung edema, vascular hyperpermeability damage, and inflammatory cell infiltration.…”

“…Given the fact of ALI/ARDS considered as an inflammatory disorder and the anti-inflammatory activity of glibenclamide, hence, glibenclamide might be against the development of ALI/ARDS in theory. In fact, a large number of studies have indicated that glibenclamide involves in the regulation of inflammation in different animal models of ALI, including oleic acid-, ozone-, radiation-, hemorrhagic shock-, and ventilator-induced ALI [11][12][13][14]. However, no such studies are reported concerning the role of glibenclamide in LPS-induced ALI.…”

The Critical Role of Potassium Efflux and Nek7 in Pasteurella multocida-Induced NLRP3 Inflammasome Activation

“…TWIK2 expressed in the plasma membrane as a K + efflux channel regulates cellular immunity, which is responsible for ATP-induced NLRP3 inflammasome activation and is sensitive to quinine (Di et al, 2018). Similarly, Glibenclamide has been also reported to attenuate the activation of NLRP3 inflammasomes by blocking K + efflux (Liu et al, 2017;Shao et al, 2020). Furthermore, Liu H. et al (2020) used Glibenclamide to block K + efflux to further study the role of K + efflux in Nek7-NLRP3 interaction.…”

Emerging Mechanisms and Targeted Therapy of Pyroptosis in Central Nervous System Trauma

“…Similarly, an active βsulfonyl nitrile called OLT1177, Marchetti et al (2018) has an anti-inflammatory effect on NLRP3 inflammasome and according to inhibits ATPase activity. Additionally, there are some other NLRP3 pathways still under study, such as Tranilast (Huang et al, 2018), Oridonin , and glyburide (Shao H et al, 2020).…”