Mechanistic insights into the role of pyroptosis in rheumatoid arthritis

Chadha, Swati; Behl, Tapan; Bungău, Simona; Kumar, Arun; Arora, Raksha; Gupta, Amit; Uddin, Sahab; Zengin, Gökhan; Aleya, Lotfi; Setia, Dhruv; Arora, Sandeep

doi:10.1016/j.retram.2020.07.003

Cited by 31 publications

(31 citation statements)

References 80 publications

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“…Besides, the DAPSA has a strong clinically significant correlation with the MDGA. In clinical practice, the assessment of the musculoskeletal disease activity 16 should include all joints, presence of enthesitis and dactylitis; however, in our study the enthesial score did not show an important relation to other clinical tools, excepting BASDAI and VAS, but it is also important to evaluate these symptoms to create the full picture of the disease.…”

Section: Discussioncontrasting

confidence: 70%

Disease activity in patients with psoriatic arthritis: a Moldavian study

Rotaru¹,

Garabajiu

Mazur-Nicorici

et al. 2021

Arch Balk Med Union

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L'activité de la maladie chez les patients avec arthrite psoriasique : une étude MoldaveIntroduction. L'arthrite psoriasique (APs) est une maladie articulaire inflammatoire qui atteint un tiers des patients avec psoriasis cutané. Les études sur l'APs ont démontré que les patients supportent une charge importante, mais celle-ci n'a pas été totalement quantifiée en raison de l'évolution variable de la maladie. Toutefois, l'applicabilité des outils cliniques existants dans l'appréciation de l'activité de la maladie doit encore être étudiée. L'objectif de l'étude a été d'évaluer le niveau d'activité de la maladie et d'apprécier la fiabilité et de l'applicabilité des mesures de l'activité de la maladie des patients avec APs. Matériel et méthodes. Nous avons effectué une étude descriptive de 46 patients avec APs. Les indices d'activité de la maladie ont été évalués et comparés. L'activité de la maladie selon chaque indice a été évaluée et l'applicabilité de ces indices a été estimée.

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Section: Discussioncontrasting

confidence: 70%

Disease activity in patients with psoriatic arthritis: a Moldavian study

Rotaru¹,

Garabajiu

Mazur-Nicorici

et al. 2021

Arch Balk Med Union

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“…RA involves erosions in the marginal bone along with the articular cartilage, leading to joint destruction. The process of pyroptosis is linked with the destruction of the plasma membrane, which releases cytokines, and excessive release of other mediators (Chadha et al, 2020;Wu et al, 2020). Active caspase-1 formation is associated with pyroptosis and inflammasome activity, and active caspase-1 takes on the role of a key housekeeping enzyme in its conversion of pro-IL-1β proteins into the active IL-1β cytokine and is measured via irreversible binding of a probe composed of an inhibitor-peptide sequence containing a fluorescent tag, referred to as FAM-FLICA (Fernandez et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Disease-Modifying Anti-rheumatic Drug Prescription Baihu-Guizhi Decoction Attenuates Rheumatoid Arthritis via Suppressing Toll-Like Receptor 4-mediated NLRP3 Inflammasome Activation

Mao

Wang

et al. 2021

Front. Pharmacol.

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As a traditional Chinese medicine-originated disease-modifying anti-rheumatic drug prescription, Baihu-Guizhi decoction (BHGZD) is extensively used for the treatment of rheumatoid arthritis (RA) with a satisfying therapeutic efficacy. Mechanically, our previous data indicated that BHGZD may ameliorate RA partially by restoring the balance of the “inflammation-immune” system through regulating the TLR4-c-Fos-IL2-TNF-alpha axis. Toll-like receptor 4 (TLR4) has been revealed to be involved in the activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome complex. Thus, the aim of the current study was to determine the regulatory effects of BHGZD on the TLR4–mediated inflammasome activation during RA progression based on the modified adjuvant-induced arthritis model (AIA-M) and the lipopolysaccharide/adenosine triphosphate (LPS/ATP)–induced pyroptosis cellular models. As a result, oral administration of BHGZD exhibited prominent improvement in the disease severity of AIA-M rats, such as reducing the redness and swelling of joints, arthritis incidence, arthritic scores, and diameter of the limb and increasing pain thresholds. In line with the in vivo findings, BHGZD treatment effectively inhibited the LPS/ATP–induced pyroptosis of both Raw264.7 macrophage and MH7A cells in vitro by reducing pyroptotic cell death morphology (swollen cells) and decreasing propidium iodide–positive and terminal deoxynucleotidyl transferase–mediated dUTP-fluorescein nick end labeling (TUNEL)–positive cells. Notably, the increased expression levels of TLR4, NLRP3, interleukin 1β, and interleukin 18 proteins and the elevated activities of caspase-1 and lactic dehydrogenase in in vivo and in vitro disease models were markedly reversed by the treatment with BHGZD. In conclusion, the above findings proved the immunomodulatory and anti-inflammatory activities of BHGZD, especially in pyroptosis, which may be attributed to the activation of TLR4–mediated NLRP3 inflammasome signaling.

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“…Piperine reportedly protected macrophages from pyroptosis in a mouse model intraperitoneally infected with Escherichia coli 33 . In a previous study, it was reported that pyroptosis plays a central role in many diseases, including osteoarthritis 49 , kidney diseases 50 , rheumatoid arthritis 51 , and COVID-19 52 . Therefore, we suspected that piperine may suppress pyroptosis in SCI.…”

Section: Discussionmentioning

confidence: 99%

Piperine Attenuates the Inflammatory Response, Oxidative Stress and Pyroptosis to Facilitate Recovery After Spinal Cord Injury via Autophagy Enhancement

Zhang

Huang

et al. 2021

Preprint

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Background: Spinal cord injury (SCI) is a serious injury that can lead to irreversible motor dysfunction and subsequently result in disability and even death. Due to its complicated pathogenic mechanism, there are no effective drug treatments. Piperine, a natural active alkaloid extracted from black pepper, suppressed inflammation in a previous study. The aim of this study was to investigate the therapeutic effect of piperine in a spinal cord injury model.Methods: Spinal cord injury was induced in C57BL/6 mice by clamping the spinal cord with a vascular clip (15 g force; Oscar) for 1 min. Eighty mice were divided randomly into the following four groups: The Sham group (n = 20), the SCI+Vehicle group (n = 20), the SCI+ Piperine group (n = 20), and the SCI+ Piperine+3MA group (n = 20). Before SCI and every 2 days post-SCI, evaluations of the Basso mouse scale (BMS) were performed. On day 14 after SCI, inclined plane tests and footprint analyses were performed. On postoperative day 3, the spinal cord was harvested to assess pyroptosis, reactive oxygen species (ROS), inflammation, and autophagy. Qualitative or quantitative analysis of the components of these potential mechanisms was performed by Western blotting (WB), immunofluorescence (IF), quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA).Results: Piperine enhanced the functional recovery of spinal cord injury. Additionally, piperine inhibited inflammation, attenuated oxidative stress and pyroptosis, and activated autophagy. However, the effects of piperine on the functional recovery of SCI, ROS-mediated autophagy, inflammation and pyroptosis were reversed by the inhibition of autophagy.Conclusions: Our experiments demonstrated that piperine facilitated the functional recovery of spinal cord injury by inhibiting the inflammatory response, oxidative stress and pyroptosis, which are mediated by the activation of autophagy.

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Mechanistic insights into the role of pyroptosis in rheumatoid arthritis

Cited by 31 publications

References 80 publications

Disease activity in patients with psoriatic arthritis: a Moldavian study

Disease activity in patients with psoriatic arthritis: a Moldavian study

Disease-Modifying Anti-rheumatic Drug Prescription Baihu-Guizhi Decoction Attenuates Rheumatoid Arthritis via Suppressing Toll-Like Receptor 4-mediated NLRP3 Inflammasome Activation

Piperine Attenuates the Inflammatory Response, Oxidative Stress and Pyroptosis to Facilitate Recovery After Spinal Cord Injury via Autophagy Enhancement

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