Arecoline increases basic fibroblast growth factor but reduces expression of <scp>IL</scp>‐1, <scp>IL</scp>‐6, G‐<scp>CSF</scp> and <scp>GM</scp>‐<scp>CSF</scp> in human umbilical vein endothelium

Ullah, Mafaz; Cox, Stephen; Kelly, Elizabeth; Moore, Malcolm A.S.; Zoellner, Hans

doi:10.1111/jop.12276

Cited by 15 publications

(10 citation statements)

References 59 publications

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“…PAI1, CSF3, and MMP9 mRNAs and protein immunoreactivity were present in endothelial cells, fibroblasts, and some leukocytes at the bottom of the wound tissue (Fig. 3), which is in accordance with the previous findings [66][67][68][69][70][71][72][73][74]. These results indicate the involvement of these cells in the wound healing process.…”

Section: Discussionsupporting

confidence: 94%

The mRNA expressions and immunohistochemistry of factors involved in angiogenesis and lymphangiogenesis in the early stage of rat skin incision wounds

Kameyama¹,

Udagawa²,

Hoshi³

et al. 2015

Legal Medicine

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Section: Discussionsupporting

confidence: 94%

The mRNA expressions and immunohistochemistry of factors involved in angiogenesis and lymphangiogenesis in the early stage of rat skin incision wounds

Kameyama¹,

Udagawa²,

Hoshi³

et al. 2015

Legal Medicine

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“…The discovery of arecoline's α7 silent agonist activity not only provides possible insight in to the mechanism for previously described effects on immune cells [ 4 , 16 , 17 , 41 – 46 ], but also provides an opportunity to refine models for the pharmacophore of α7 silent agonism in regard to comparisons with the other muscarinic activators tested.…”

Section: Discussionmentioning

confidence: 99%

Nicotinic Activity of Arecoline, the Psychoactive Element of "Betel Nuts", Suggests a Basis for Habitual Use and Anti-Inflammatory Activity

2015

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Habitual chewing of "betel nut" preparations constitutes the fourth most common human self-administration of a psychoactive substance after alcohol, caffeine, and nicotine. The primary active ingredient in these preparations is arecoline, which comes from the areca nut, the key component of all such preparations. Arecoline is known to be a relatively non-selective muscarinic partial agonist, accounting for many of the overt peripheral and central nervous system effects, but not likely to account for the addictive properties of the drug. We report that arecoline has activity on select nicotinic acetylcholine receptor (nAChR) subtypes, including the two classes of nAChR most related to the addictive properties of nicotine: receptors containing α4 and β2 subunits and those which also contain α6 and β3 subunits. Arecoline is a partial agonist with about 6–10% efficacy for the α4* and α6* receptors expressed in Xenopus oocytes. Additionally, arecoline is a silent agonist of α7 nAChR; while it does not activate α7 receptors when applied alone, it produces substantial activation when co-applied with the positive allosteric modulator PNU-120696. Some α7 silent agonists are effective inhibitors of inflammation, which might account for anti-inflammatory effects of arecoline. Arecoline's activity on nAChR associated with addiction may account for the habitual use of areca nut preparations in spite of the well-documented risk to personal health associated with oral diseases and cancer. The common link between betel and tobacco suggests that partial agonist therapies with cytisine or the related compound varenicline may also be used to aid betel cessation attempts.

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“…Lung tissue was collected (approximately 50 mg) and total messenger RNA (mRNA) was isolated using TRIzol (Thermo Fisher) and complementary DNA (cDNA) was acquired through the use of a qScript cDNA Synthesis Kit (Quanta Biosciences, Germany) according to the manufacturer’s protocols. The primers for metallothionein-1, G-CSF, TNFα, the zinc transporters and the housekeeping gene glycerinaldehyde 3-phosphate dehydrogenase (GAPDH)15 30–32 were used as previously described. All samples were run in duplicate using a Step-1 (metallothionein(MT)-1, zinc transporters, GAPDH) or QuantStudio 3 (TNFα, G-CSF, GAPDH) 15.…”

Section: Methodsmentioning

confidence: 99%

Zinc supplementation ameliorates lung injury by reducing neutrophil recruitment and activity

Weßels

Pupke

Trotha

et al. 2020

Thorax

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IntroductionZinc is well known for its anti-inflammatory effects, including regulation of migration and activity of polymorphonuclear neutrophils (PMN). Zinc deficiency is associated with inflammatory diseases such as acute lung injury (ALI). As deregulated neutrophil recruitment and their hyper-activation are hallmarks of ALI, benefits of zinc supplementation on the development of lipopolysaccharides (LPS)-induced ALI were tested.Methods64 C57Bl/6 mice, split into eight groups, were injected with 30 µg zinc 24 hours before exposure to aerosolised LPS for 4 hours. Zinc homoeostasis was characterised measuring serum and lung zinc concentrations as well as metallothionein-1 expression. Recruitment of neutrophils to alveolar, interstitial and intravascular space was assessed using flow cytometry. To determine the extent of lung damage, permeability and histological changes and the influx of protein into the bronchoalveolar lavage fluid were measured. Inflammatory status and PMN activity were evaluated via tumour necrosis factor α levels and formation of neutrophil extracellular traps. The effects of zinc supplementation prior to LPS stimulation on activation of primary human granulocytes and integrity of human lung cell monolayers were assessed as well.ResultsInjecting zinc 24 hours prior to LPS-induced ALI indeed significantly decreased the recruitment of neutrophils to the lungs and prevented their hyperactivity and thus lung damage was decreased. Results from in vitro investigations using human cells suggest the transferability of the finding to human disease, which remains to be tested in more detail.ConclusionZinc supplementation attenuated LPS-induced lung injury in a murine ALI model. Thus, the usage of zinc-based strategies should be considered to prevent detrimental consequences of respiratory infection and lung damage in risk groups.

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Arecoline increases basic fibroblast growth factor but reduces expression of IL‐1, IL‐6, G‐CSF and GM‐CSF in human umbilical vein endothelium

Abstract: Data raise the possibility that arecoline-induced, vascular basic fibroblast growth factor contributes to OSF, by combining increased growth factor expression with endothelial necrosis, and thus driving fibroblast proliferation.

Cited by 15 publications

References 59 publications

The mRNA expressions and immunohistochemistry of factors involved in angiogenesis and lymphangiogenesis in the early stage of rat skin incision wounds

The mRNA expressions and immunohistochemistry of factors involved in angiogenesis and lymphangiogenesis in the early stage of rat skin incision wounds

Nicotinic Activity of Arecoline, the Psychoactive Element of "Betel Nuts", Suggests a Basis for Habitual Use and Anti-Inflammatory Activity

Zinc supplementation ameliorates lung injury by reducing neutrophil recruitment and activity

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