Publication Details |
| Category | Text Publication |
| Reference Category | Journals |
| DOI | 10.1016/j.scitotenv.2023.169650 |
| Title (Primary) | Triclosan and its alternatives, especially chlorhexidine, modulate macrophage immune response with distinct modes of action |
| Author | Raps, S.; Bahr, L.; Karkossa, I.; Rossol, M.; von Bergen, M.; Schubert, K. |
| Source Titel | Science of the Total Environment |
| Year | 2024 |
| Department | MOLTOX |
| Volume | 941 |
| Page From | art. 169650 |
| Language | englisch |
| Topic | T9 Healthy Planet |
| Data and Software links | https://doi.org/10.6019/PXD044828 |
| Keywords | Triclosan; Chlorhexidine; Macrophages; Primary human monocytes; Inflammasome; Proteomics |
| Abstract | Since European regulators
restricted the use of bacteriocidic triclosan (TCS), alternatives for TCS are
emerging. Recently, TCS has been shown to reprogram immune metabolism, trigger
the NLRP3 inflammasome, and subsequently the release of IL-1β in human macrophages, but data on
substitutes is scarce. Hence, we aimed to examine the effects of TCS compared
to its alternatives at the molecular level in human macrophages. LPS-stimulated THP-1 macrophages were exposed to TCS or its substitutes, including benzalkonium chloride, benzethonium chloride, chloroxylenol, chlorhexidine (CHX) and cetylpyridinium chloride, with the inhibitory concentration (IC10-value) of cell viability to decipher their mode of action. TCS induced the release of the pro-inflammatory cytokine TNF and high level of IL-1β, suggesting the activation of the NLRP3-inflammasome, which was confirmed by non-apparent IL-1β under the NLRP3-inhibitor MCC950 treatment d. While IL-6 release was reduced in all treatments, the alternative CHX completely abolished the release of all investigated cytokines. To unravel the underlying molecular mechanisms, we used untargeted LC-MS/MS-based proteomics. TCS and CHX showed the strongest cellular response at the protein and signalling pathway level, whereby pathways related to metabolism, translation, cellular stress and migration were mainly affected but to different proposed modes of action. TCS inhibited mitochondrial electron transfer and affected phagocytosis. In contrast, in CHX-treated cells, the translation was arrested due to stress conditions, resulting in the formation of stress granules. Mitochondrial (e.g. ATP5F1D, ATP5PB, UQCRQ) and ribosomal (e.g. RPL10, RPL35, RPS23) proteins were revealed as putative key drivers. Furthermore, we have demonstrated the formation of podosomes by CHX, potentially involved in ECM degradation. Our results exhibit modulation of the immune response in macrophages by TCS and its substitutes and illuminated underlying molecular effects. These results illustrate critical processes involved in the modulation of macrophages' immune response by TCS and its alternatives, providing information essential for hazard assessment. |
| Persistent UFZ Identifier | https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=28578 |
| Raps, S., Bahr, L., Karkossa, I., Rossol, M., von Bergen, M., Schubert, K. (2024): Triclosan and its alternatives, especially chlorhexidine, modulate macrophage immune response with distinct modes of action Sci. Total Environ. 941 , art. 169650 10.1016/j.scitotenv.2023.169650 |
|