Polyhexamethylene Guanidine Phosphate Damages Tight Junctions and the F-Actin Architecture by Activating Calpain-1 via the P2RX7/Ca2+ Signaling Pathway

Abstract

Polyhexamethylene guanidine phosphate (PHMG-p), a member of the polymeric guanidine family, has strong antimicrobial activity and may increase the risk of inflammation-associated pulmonary fibrosis. However, the effect of PHMG-p on the barrier function of the bronchial epithelium is unknown. Epithelial barrier functioning is maintained by tight junctions (TJs); damage to these TJs is the major cause of epithelial barrier breakdown during lung inflammation. The present study showed that, in BEAS-2B human bronchial epithelial cells, exposure to PHMG-p reduced the number of TJs and the E-cadherin level and impaired the integrity of the F-actin architecture. Furthermore, exposure to PHMG-p stimulated the calcium-dependent protease calpain-1, which breaks down TJs. However, treatment with the calpain-1 inhibitor, ALLN, reversed the PHMG-p-mediated impairment of TJs and the F-actin architecture. Furthermore, exposure to PHMG-p increased the intracellular Ca2+ level via P2X purinoreceptor 7 (P2RX7) and inhibition of P2RX7 abolished the PHMG-p-induced calpain-1 activity and protein degradation and increased the intracellular Ca2+ level. Although exposure to PHMG-p increased the extracellular ATP level, hydrolysis of extracellular ATP by apyrase did not influence its detrimental effect on bronchial epithelial cells. These results implicate the impairment of TJs and the F-actin architecture in the pathogenesis of pulmonary diseases.

trans-Fatty acids promote p53-dependent apoptosis triggered by cisplatin-induced DNA interstrand crosslinks via the Nox-RIP1-ASK1-MAPK pathway

“…S7 online). These data suggest a specific requirement of RIP1 for cell death induced by CDDP, in agreement with the previous reports 25 , 32 , 33 . Moreover, we showed that RIP1 deficiency strongly inhibited CDDP-induced ROS generation irrespective of the presence of EA (Fig.…”

Aesculetin Attenuates Alveolar Injury and Fibrosis Induced by Close Contact of Alveolar Epithelial Cells with Blood-Derived Macrophages via IL-8 Signaling

“…Recent studies have reported that the instillation of PHMG used as a humidifier disinfectant, induces irreversible pulmonary injury and lung fibrosis [ 27 , 44 ]. There were inflammatory macrophage infiltration, bronchiolo-alveolar epithelial hyperplasia and pulmonary fibrosis mainly observed in the terminal bronchioles and alveoli in the lungs of PHMG-loaded mice [ 27 ].…”

“…Similarly, this study found that the PHMG inhalation of mice enhanced macrophage infiltration into the alveolar space, indicating that continuous inflammatory responses by PHMG may contribute to the development of pulmonary fibrosis. Furthermore, PHMG phosphate results in damage of tight junctions and impairment of F-actin architecture integrity in human bronchial epithelial cells [ 44 ]. In the current study, PHMG inhalation stimulated the EMT process and thereby loss of tight junction proteins in lungs.…”

Disinfection of Ready-to-Eat Lettuce Using Polyhexamethylene Guanidine Hydrochloride

“…Untreated samples were used as a control group. Sanitizer was diluted with tap water (20 ± 2 • C) to prepare the disinfection Microorganisms 2020, 8,272 3 of 9 solution. The free chlorine concentration was adjusted as desired using a Free Chlorine Test Kit (Lohand, Hangzhou, China).…”

“…Polyhexamethylene guanidine hydrochloride (PHMG) is a member of the polymeric guanidine family and shows low toxicity. It has broad in vitro bactericidal activity against Gram-positive and Gram-negative bacteria as well as fungi [8]. Its main antibacterial mechanism is collapse of the outer membrane structure, leading to the formation of a pore across the membrane [9,10] and subsequent DNA damage [11].…”