Triclosan disrupts immune cell function by depressing Ca2+ influx following acidification of the cytoplasm

Sangroula, Suraj; Vasquez, Alan Y. Baez; Raut, Prakash; Obeng, Bright; Shim, Juyoung; Bagley, Grace D.; West, Bailey E.; Burnell, John E.; Kinney, Marissa S.; Potts, Christian M.; Weller, Sasha R.; Kelley, Joshua B.; Hess, Samuel T.; Gosse, Julie A.

doi:10.1016/j.taap.2020.115205

Cited by 18 publications

(17 citation statements)

References 125 publications

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“…Localized molecular coordinates of HA-Dendra2 and PAmKate-PH were then quantified using SLCA (Curthoys et al, 2019;Sangroula et al, 2020;Sneath, 1957) to determine the properties of clusters formed by the HA and PH domain.…”

Section: Discussionmentioning

confidence: 99%

“…We used super-resolution microscopy (FPALM) to image HA-Dendra2 and the PIP 2 -binding PH domain tagged with PAmKate (Flesch et al , 2005; Szentpetery et al , 2009; Curthoys et al , 2019) (Figure 6). Localized molecular coordinates of HA-Dendra2 and PAmKate-PH were then quantified using SLCA (Curthoys et al , 2019; Sangroula et al , 2020; Sneath, 1957) to determine the properties of clusters formed by the HA and PH domain.…”

Section: Discussionmentioning

confidence: 99%

“…Two color FPALM was performed by previously published methods (Hess et al , 2006; Gunewardene et al , 2011; Curthoys et al , 2019; Sangroula et al , 2020). Briefly, lasers with wavelengths λ = 405 nm (CrystaLaser, 5mW) for the activation of Dendra2 molecule (Gurskaya et al, 2006) and λ = 558 nm for the readout (CrystaLaser, 100 mW) were focused in the back-aperture plane of an oil immersion objective (Olympus 60X 1.45NA) using a second lens (f = 350 mm, Thorlabs) at one focal length away from the back aperture.…”

Section: Methodsmentioning

confidence: 99%

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Cetylpyridinium chloride (CPC) reduces zebrafish mortality from influenza infection: Super-resolution microscopy reveals CPC interference with multiple protein interactions with phosphatidylinositol 4,5-bisphosphate in immune function

Raut

Weller

Obeng

et al. 2021

Preprint

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The COVID-19 pandemic raises significance for a potential influenza therapeutic compound, cetylpyridinium chloride (CPC), which has been extensively used in personal care products as a positively-charged quaternary ammonium antibacterial agent. CPC is currently in clinical trials to assess its effects on severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) morbidity. Two published studies have provided mouse and human data indicating that CPC may alleviate influenza infection, and here we show that CPC (0.1 uM, 1 hour) reduces zebrafish mortality and viral load following influenza infection. However, CPC mechanisms of action upon viral-host cell interaction are currently unknown. We have utilized super-resolution fluorescence photoactivation localization microscopy to probe the mode of CPC action. Reduction in density of influenza viral protein hemagglutinin (HA) clusters is known to reduce influenza infectivity: here, we show that CPC (at non-cytotoxic doses, 5-10 uM) reduces HA density and number of HA molecules per cluster within the plasma membrane of NIH-3T3 mouse fibroblasts. HA is known to colocalize with the negatively-charged mammalian lipid phosphatidylinositol 4,5-bisphosphate (PIP2); here, we show that nanoscale co-localization of HA with the PIP2-binding Pleckstrin homology (PH) reporter in the plasma membrane is diminished by CPC. CPC also dramatically displaces the PIP2-binding protein myristoylated alanine-rich C-kinase substrate (MARCKS) from the plasma membrane of rat RBL-2H3 mast cells; this disruption of PIP2 is correlated with inhibition of mast cell degranulation. Together, these findings offer a PIP2-focused mechanism underlying CPC disruption of influenza and suggest potential pharmacological use of this drug as an influenza therapeutic to reduce global deaths from viral disease.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Cetylpyridinium chloride (CPC) reduces zebrafish mortality from influenza infection: Super-resolution microscopy reveals CPC interference with multiple protein interactions with phosphatidylinositol 4,5-bisphosphate in immune function

Raut

Weller

Obeng

et al. 2021

Preprint

Self Cite

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“…TCS-induced inflammasome activation led to chemokine release -Cxcl1/2, Ccl2, and Ccl19 in the dLN and Cxcl1/2 in the skin. In the mice model, TCS led to activation of the NLRP3 inflammasome by another pathway -increasing Drp1 and decreasing Opa1 expression [19]. The dynamin-related protein 1 (Drp 1) is associated with mitochondrial fission and the role of optic atrophy 1 (Opa1) is maintenance of the structure of the inner mitochondrial membrane [18].…”

Section: Description Of the State Of Knowledgementioning

confidence: 99%

“…Mitochondrial toxicity of TCS is related to inflammation and immunity [19]. Due to its proton ionophore nature, it…”

Section: Description Of the State Of Knowledgementioning

confidence: 99%

Mechanism of action of triclosan as an endocrine-disrupting chemical with its impact on human health – literature review

Maksymowicz¹,

Machowiec²,

Ręka³

et al. 2021

J Pre Clin Clin Res.

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Introduction and objective.Triclosan is a synthetic, aromatic organic chemical compound with antimicrobial properties. Due to its wide application as a preservative in cosmetics, antiperspirants, plastics, or surgical sutures, various mechanisms of TCS action on the human body are described. The study focus on the analysis of antimicrobial properties, effects on metabolism, immunity and the endocrine system, as well as carcinogenesis. Review methods. The latest literature available on 13 June 2021 was reviewed by using the PubMed and Google Scholar databases. There were 34 papers selected for analysis after reading the abstracts, which met the assumed criteria. Brief description of the state of knowledge. Triclosan can be used as an antimicrobial against bacteria such as Staphylococcus aureus, Mycobacterium tuberculosis. However, over-exposure to TCS can also contribute to the acquisition of resistance in bacteria. Interestingly, triclosan as an endocrine disrupting chemical (EDC) might disrupt thyroid, ovarian, or testis homeostasis, having a potential impact on reproductive health. TCS via an estrogen receptor signaling pathway can raise estrogen and progesterone secretion and promote development of hormone-dependent neoplasms, such as breast and ovarian cancer. The chemical has also potential to induce cell proliferation of prostate cancer cells. On the other hand, it contributes to apoptosis in Burkitt lymphoma-derived cells, which means that TCS can have antitumour properties. Conclusion.Triclosan is a commonly usean antimicrobial agent in medical and consumer care products. Due to its unclear impact on organisms, further studies are necessary regarding both the use of TCS as an antibacterial agent and possible harmful effects on the human body.

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Engineering silver nanoparticle surfaces for antimicrobial applications

Niyonshuti

Rogers²,

Okyere³

et al. 2023

Encyclopedia of Nanomaterials

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Triclosan disrupts immune cell function by depressing Ca2+ influx following acidification of the cytoplasm

Cited by 18 publications

References 125 publications

Cetylpyridinium chloride (CPC) reduces zebrafish mortality from influenza infection: Super-resolution microscopy reveals CPC interference with multiple protein interactions with phosphatidylinositol 4,5-bisphosphate in immune function

Cetylpyridinium chloride (CPC) reduces zebrafish mortality from influenza infection: Super-resolution microscopy reveals CPC interference with multiple protein interactions with phosphatidylinositol 4,5-bisphosphate in immune function

Mechanism of action of triclosan as an endocrine-disrupting chemical with its impact on human health – literature review

Engineering silver nanoparticle surfaces for antimicrobial applications

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