Synergistic Effects of Ethanol and Isopentenyl Pyrophosphate on Expansion of γδ T Cells in Synovial Fluid from Patients with Arthritis

Laurent, Agneta J.; Bindslev, Niels; Johansson, Björn; Berg, Louise

doi:10.1371/journal.pone.0103683

Cited by 3 publications

(5 citation statements)

References 49 publications

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“…14 We have earlier shown that around 2.5 mM ethanol can enhance the expansion of γδ T cells stimulated with isopentenylpyrophosphate. 16 We expected to find an enhancing effect of alcohol on iso-α-acid-stimulated SH-SY5Y and NES cells, as well. Surprisingly, there was no enhancing effect in the concentration range relevant for beer drinking, and this can explain why the effects on cell expansion are similar for nonalcoholic and alcoholic beer (Figure 6).…”

Section: ■ Discussionsupporting

confidence: 90%

“…Thirty minutes after drinking two bottles of alcoholic beer (5.3% ABV), the blood alcohol concentration is 32 mg/100 mL, and two bottles would equal around 6–7 mM . We have earlier shown that around 2.5 mM ethanol can enhance the expansion of γδ T cells stimulated with isopentenylpyrophosphate . We expected to find an enhancing effect of alcohol on iso-α-acid-stimulated SH-SY5Y and NES cells, as well.…”

Section: Discussionmentioning

confidence: 99%

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Iso-α-acids in Nonalcoholic and Alcoholic Beer Stimulate Growth of Neuron-like SH-SY5Y Cells and Neuroepithelial Stem Cells

Laurent

Bindslev

Vukojević

et al. 2021

ACS Bio Med Chem Au

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With the increasing popularity of nonalcoholic beer, the association between beer drinking and alcohol intake is lost. In the present study, we show that nonalcoholic beer can stimulate the expansion of neuron-like cell lines and neuroepithelial stem cells in culture, yielding an effect comparable to that of alcoholic beer. One ingredient in beer is hops, which is derived from the flower of hop plants. The female flower contains humulones, which are transformed into iso-α-acids during wort boiling and give beer its bitter taste. In this study, we tested the effects of these iso-α-acids and/or alcohol on the proliferation of neuron-like cells and neuroepithelial stem cells in culture. Iso-α-acids enhanced cell expansion, showing a bimodal dose–response curve with peaks around 2–30 nM and 2–5 μM, of which nanomolar concentrations are relevant in beer drinking. The more lipophilic trans-iso-α-acids, found to a greater extent in beer foam, are even more potent. Our results indicate that iso-α-acids, acting via peroxisome proliferator-activated receptors could be responsible for the observed effects. Altogether, our results indicate that nonalcoholic beer with ingredients such as iso-α-acids stimulate the proliferation of neuroepithelial stem cells.

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Section: ■ Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Iso-α-acids in Nonalcoholic and Alcoholic Beer Stimulate Growth of Neuron-like SH-SY5Y Cells and Neuroepithelial Stem Cells

Laurent

Bindslev

Vukojević

et al. 2021

ACS Bio Med Chem Au

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“…In a pioneering study, clones from rheumatoid synovium expressing Vγ9δ2 were shown to respond to synthetic alkyl phosphates and particularly to monoethyl phosphate (MEP) [45]. Later on, γδ T cells from synovial fluid were also shown to be reactive to isopentenyl pyrophosphate (IPP), an important endogenously produced phosphoantigen and an additive effect of a low dose of ethanol increased IPP induced proliferation of synovial γδ T cells, with similar findings applying to normal PB γδ T cells [46]. Other antigens for RA derived γδ T cells have been reported sporadically.…”

Section: Responses To Putative Antigenmentioning

confidence: 80%

The Role of Gamma Delta T Cells in Autoimmune Rheumatic Diseases

Bank

2020

Cells

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Autoimmune rheumatic diseases (ARDs), affecting ~1–1.5% of all humans, are associated with considerable life long morbidity and early mortality. Early studies in the 1990s showed numerical changes of the recently discovered γδ T cells in the peripheral blood and in affected tissues of patients with a variety of ARDs, kindling interest in their role in the immuno-pathogenesis of these chronic inflammatory conditions. Indeed, later studies applied rapid developments in the understanding of γδ T cell biology, including antigens recognized by γδ T cells, their developmental programs, states of activation, and cytokine production profiles, to analyze their contribution to the pathological immune response in these disorders. Here we review the published studies addressing the role of γδ T in the major autoimmune rheumatic diseases, including rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, systemic lupus erythematosus and scleroderma, and animal models thereof. Due to their unique properties spanning adaptive and innate immune functions, the ever deeper understanding of this unique T cell population is shedding new light on the pathogenesis of, while potentially enabling new therapeutic approaches to, these diseases.

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“…Moreover, these expanded γδ T cells might target fibroblast-like synoviocytes, explaining the substantial protective effects of ethanol against RA and other autoimmune disorders. 139 140 In response to TCR activation, GGPP promotes cell proliferation, but its precursor, specifically farnesyl-PP, may reduce phosphorylation of p38 and ERK to regulate c-Fos-oriented DNA binding. 113 Rheumatoid fibroblastlike synoviocytes secreting pentraxin 3 and monocyte chemoattractant protein-1 respond to geranylgeranylpyrophosphate via a Rho-dependent mechanism.…”

Section: Ippmentioning

confidence: 99%

“…A substantial increase in γδ T cells in synovial fluid from arthritis patients is amplified by ethanol and isopentenyl pyrophosphate, indicating that ethanol concentrations, which further enhance IPP‐stimulated expansion of γδ T cells. Moreover, these expanded γδ T cells might target fibroblast‐like synoviocytes, explaining the substantial protective effects of ethanol against RA and other autoimmune disorders 139 …”

Section: Mevalonate Pathway and Autoimmune Diseasesmentioning

confidence: 99%

Old and new damage‐associated molecular patterns (DAMPs) in autoimmune diseases

Kang

Liu

Haneef

et al. 2022

Rheumatology & Autoimmunity

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All organisms living in complex environments have evolved effective mechanisms of dynamic responses to extracellular stimuli. The immune system activates when damaged or injured cells release damage-associated molecular patterns (DAMPs). In addition to well-characterized DAMPs such as high-mobility group box 1 and adenosine triphosphate, studies on new classes of DAMPs have emerged. Here, we review recent reports of a new class of isoprenoid-derived DAMPs, including farnesyl pyrophosphate and geranylgeranyl pyrophosphate, both of which are pivotal metabolic intermediates of the mevalonate pathway. We also explore the roles of old and new DAMPs in autoimmune diseases that result from dysregulated inflammation. The findings highlight that understanding the functional mechanisms of DAMPs is important to enrich the DAMP family and decipher their immunoregulatory mechanisms to provide new therapeutics for the prevention and treatment of autoimmune diseases.

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Synergistic Effects of Ethanol and Isopentenyl Pyrophosphate on Expansion of γδ T Cells in Synovial Fluid from Patients with Arthritis

Cited by 3 publications

References 49 publications

Iso-α-acids in Nonalcoholic and Alcoholic Beer Stimulate Growth of Neuron-like SH-SY5Y Cells and Neuroepithelial Stem Cells

Iso-α-acids in Nonalcoholic and Alcoholic Beer Stimulate Growth of Neuron-like SH-SY5Y Cells and Neuroepithelial Stem Cells

The Role of Gamma Delta T Cells in Autoimmune Rheumatic Diseases

Old and new damage‐associated molecular patterns (DAMPs) in autoimmune diseases

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