Cannabidiol Modifies the Formation of NETs in Neutrophils of Psoriatic Patients

Wójcik, Piotr; Garley, Marzena; Wroński, Adam; Jabłońska, Ewa; Skrzydlewska, Elżbieta

doi:10.3390/ijms21186795

Cited by 19 publications

(17 citation statements)

References 61 publications

(85 reference statements)

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“…and Leon et al. ( 24 , 25 ) In the current analysis, we did not find the correlation between PASI score and serum MPO–DNA in patients with PsA. We reckon that NETosis takes part in different pathogenesis pathways in psoriasis and PsA.…”

Section: Discussioncontrasting

confidence: 69%

NETosis in Psoriatic Arthritis: Serum MPO–DNA Complex Level Correlates With Its Disease Activity

Yang

et al. 2022

Front. Immunol.

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BackgroundNeutrophil extracellular trap formation (NETosis) has been rarely reported in psoriatic arthritis (PsA). We aimed to explore the involvement of NETosis in the inflammation of PsA.MethodsSerum myeloperoxidase–DNA (MPO-DNA) complex was detected by a modified enzyme-linked immunosorbent assay and compared among 74 patients with PsA, 58 patients with psoriasis (PsO), and 20 healthy controls. The association of MPO–DNA level with disease activity index at baseline and follow-up was analyzed in patients with PsA. Receiver operating characteristic curve was used to evaluate the predictive value of MPO–DNA for treatment response.ResultsMPO–DNA complex level in serum was significantly increased in patients with PsA/PsO compared to healthy controls (p < 0.001). The level of MPO–DNA was positively associated with DAPSA score and its components (including TJC, SJC, PGA, VAS-pain and CRP, r = 0.25–0.409, all p-values < 0.05). Serum MPO–DNA level was downregualted at 12 weeks after treatment compared to baseline (p = 0.022). The decrease of MPO–DNA level was more dramatic in patients with PsA who achieved both ACR50 and PASI50 response than those achieving neither of them at 12 weeks (p = 0.023). ROC analysis revealed that the serum MPO–DNA level predicted both ACR50 and PASI50 achievement at week 12 (p = 0.04; 95% CIs, 0.56–0.94). Moreover, the baseline MPO–DNA level (p = 0.009; 95% CIs, 0.748–1) and change of MPO–DNA at week 12 from baseline (p = 0.004; 95% CIs, 0.802–1) were associated with the achievement of both ACR70 and PASI75 response at week 24.ConclusionsNETosis plays an important role in psoriatic diseases. The level of MPO–DNA complex in serum reflects disease activity. Serum MPO–DNA complex may be a useful biomarker to predict the therapeutic response in PsA.

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Section: Discussioncontrasting

confidence: 69%

NETosis in Psoriatic Arthritis: Serum MPO–DNA Complex Level Correlates With Its Disease Activity

Yang

et al. 2022

Front. Immunol.

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“…CBD has also been shown to increase the oxygen consumption rate and enhance mitochondrial bioenergetics [ 190 ], and at high concentrations can promote COX-2 expression in LPS-treated macrophages [ 216 ]. In further support of the pro-oxidant capacity of CBD, it is also important to note that CBD has been shown to increase the expression of the NOX4 and p22phox NAP(P)H oxidases [ 208 ], and also enhances the production of the p47 subunit of pro-oxidative NADPH oxidase in endotoxin-treated neutrophils from healthy subjects [ 217 ]. Finally, CBD promotes a reduction in GSH in splenocytes [ 209 ] and has been shown to deplete GSH in human gliomas [ 214 ].…”

Section: Antioxidant Mechanisms Of Action Of Cbdmentioning

confidence: 99%

Cannabidiol modulation of oxidative stress and signalling

et al. 2021

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Cannabidiol (CBD), one of the primary non-euphoric components in the Cannabis sativa L. plant, has undergone clinical development over the last number of years as a therapeutic for patients with Lennox-Gastaut syndrome and Dravet syndromes. This phytocannabinoid demonstrates functional and pharmacological diversity, and research data indicate that CBD is a comparable antioxidant to common antioxidants. This review gathers the latest knowledge regarding the impact of CBD on oxidative signalling, with focus on the proclivity of CBD to regulate antioxidants and control the production of reactive oxygen species. CBD is considered an attractive therapeutic agent for neuroimmune disorders, and a body of literature indicates that CBD can regulate redox function at multiple levels, with a range of downstream effects on cells and tissues. However, pro-oxidant capacity of CBD has also been reported, and hence caution must be applied when considering CBD from a therapeutic standpoint. Such pro- and antioxidant functions of CBD may be cell- and model-dependent, and may also be influenced by CBD dose, the duration of CBD treatment and the underlying pathology.

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“…General pustular psoriasis (GPP) is an acute and severe systemic inflammation characterized by neutrophilic-rich dysfunction, leading to sterile pustules in skin lesions. It was triggered by neutrophil extracellular traps (NETs) formation (termed as NETosis, a cell death process), which is implicated in autoimmune inflammatory reactions and induced by neutrophil activation and respiratory burst, to release the non-specific effects of CitH3, enzymatic proteins (like neutrophil elastase and MPO), cytosolic proteins (such as S100 calcium-binding proteins) and recruit pro-inflammatory immune cells [ 84 – 87 ]. The process of NETosis mediated by reactive oxygen species (ROS)-derived from mitochondria and NADPH oxidase could induce autoantibody production, resulting in uncontrolled inflammatory response and tissue pathology [ 88 ].…”

Section: Oxidative Stress and Its Roles In Different Cell Types Dysfu...mentioning

confidence: 99%

Advances in the modulation of ROS and transdermal administration for anti-psoriatic nanotherapies

Chen

Qian

et al. 2022

J Nanobiotechnol

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Reactive oxygen species (ROS) at supraphysiological concentration have a determinate role in contributing to immuno-metabolic disorders in the epithelial immune microenvironment (EIME) of psoriatic lesions. With an exclusive focus on the gene-oxidative stress environment interaction in the EIME, a comprehensive strategy based on ROS-regulating nanomedicines is greatly anticipated to become the mainstay of anti-psoriasis treatment. This potential therapeutic modality could inhibit the acceleration of psoriasis via remodeling the redox equilibrium and reshaping the EIME. Herein, we present a marked overview of the current progress in the pathomechanisms of psoriasis, with particular concerns on the potential pathogenic role of ROS, which significantly dysregulates redox metabolism of keratinocytes (KCs) and skin-resident or -infiltrating cells. Meanwhile, the emergence of versatile nanomaterial-guided evolution for transdermal drug delivery has been attractive for the percutaneous administration of antipsoriatic therapies in recent years. We emphasize the underlying molecular mechanism of ROS-based nanoreactors for improved therapeutic outcomes against psoriasis and summarize up-to-date progress relating to the advantages and limitations of nanotherapeutic application for transdermal administration, as well as update an insight into potential future directions for nanotherapies in ROS-related skin diseases. Graphical Abstract

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Cannabidiol Modifies the Formation of NETs in Neutrophils of Psoriatic Patients

Cited by 19 publications

References 61 publications

NETosis in Psoriatic Arthritis: Serum MPO–DNA Complex Level Correlates With Its Disease Activity

NETosis in Psoriatic Arthritis: Serum MPO–DNA Complex Level Correlates With Its Disease Activity

Cannabidiol modulation of oxidative stress and signalling

Advances in the modulation of ROS and transdermal administration for anti-psoriatic nanotherapies

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