Simultaneous Activation of Mu and Delta Opioid Receptors Reduces Allodynia and Astrocytic Connexin 43 in an Animal Model of Neuropathic Pain

Vicario, Nunzio; Pasquinucci, Lorella; Spitale, Federica Maria; Chiechio, Santina; Turnaturi, Rita; Caraci, Filippo; Tibullo, Daniele; Avola, Roberto; Gulino, Rosario; Parenti, Rosalba; Parenti, Carmela

doi:10.1007/s12035-019-1607-1

Cited by 45 publications

(42 citation statements)

References 70 publications

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“…All together these complex series of biochemical events lead to the activation of the inflammasome and induce an immune response inhibiting pathogen replication [ 23 , 25 , 26 , 27 ] ( Figure 1 B). Intracellular danger signals (danger-associated molecular patterns) released from damaged or dying cells are also able to activate inflammasomes, but impaired inflammasome signaling causes and hyperinflammatory state, leading to the development of autoimmune and neurodegenerative diseases and cancer progression [ 28 , 29 , 30 , 31 , 32 , 33 ].…”

Section: Introductionmentioning

confidence: 99%

The Role of Inflammation and Inflammasome in Myeloproliferative Disease

Longhitano

Volti

Giallongo

et al. 2020

JCM

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Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are rare hematological conditions known as myeloproliferative neoplasms (MPNs). They are characterized for being BCR-ABL negative malignancies and affected patients often present with symptoms which can significantly impact their quality of life. MPNs are characterized by a clonal proliferation of an abnormal hematopoietic stem/progenitor cell. In MPNs; cells of all myeloid lineages; including those involved in the immune and inflammatory response; may belong to the malignant clone thus leading to an altered immune response and an overexpression of cytokines and inflammatory receptors; further worsening chronic inflammation. Many of these cytokines; in particular, IL-1β and IL-18; are released in active form by activating the inflammasome complexes which in turn mediate the inflammatory process. Despite this; little is known about the functional effects of stem cell-driven inflammasome signaling in MPN pathogenesis. In this review we focused on the role of inflammatory pathway and inflammasome in MPN diseases. A better understanding of the inflammatory-state-driving MPNs and of the role of the inflammasome may provide new insights on possible therapeutic strategies

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Section: Introductionmentioning

confidence: 99%

The Role of Inflammation and Inflammasome in Myeloproliferative Disease

Longhitano

Volti

Giallongo

et al. 2020

JCM

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“…PCA was performed as previously described [52][53][54]. Briefly, loading individual metabolite levels per sample per group.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of TLR4 Signaling Affects Mitochondrial Fitness and Overcomes Bortezomib Resistance in Myeloma Plasma Cells

Giallongo

Tibullo

Puglisi

et al. 2020

Cancers

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Multiple myeloma (MM) is a B-cell malignancy requiring inflammatory microenvironment signals for cell survival and proliferation. Despite improvements in pharmacological tools, MM remains incurable mainly because of drug resistance. The present study aimed to investigate the implication of Toll-like receptor 4 (TLR4) as the potential mechanism of bortezomib (BTZ) resistance. We found that TLR4 activation induced mitochondrial biogenesis and increased mitochondrial mass in human MM cell lines. Moreover, TLR4 signaling was activated after BTZ exposure and was increased in BTZ-resistant U266 (U266-R) cells. A combination of BTZ with TAK-242, a selective TLR4 inhibitor, overcame drug resistance through the generation of higher and extended oxidative stress, strong mitochondrial depolarization and severe impairment of mitochondrial fitness which in turn caused cell energy crisis and activated mitophagy and apoptosis. We further confirmed the efficacy of a TAK-242/BTZ combination in plasma cells from refractory myeloma patients. Consistently, inhibition of TLR4 increased BTZ-induced mitochondrial depolarization, restoring pharmacological response. Taken together, these findings indicate that TLR4 signaling acts as a stress-responsive mechanism protecting mitochondria during BTZ exposure, sustaining mitochondrial metabolism and promoting drug resistance. Inhibition of TLR4 could be therefore be a possible target in patients with refractory MM to overcome BTZ resistance.

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“…In particular, many data literature reported that the colon cancer is strongly associated with obesity and body weight (Dore et al, 2020). Furthermore, the production of pro-inflammatory cytokines is a characteristic of chronic low inflammation of obese subjects and is strongly involved also in oxidative stress and ROS production (Vicario et al, 2019;Di Mauro et al, 2019;Mauri et al, 2019). The obesity is a multifactorial disease, and it is evidenced that the healthy lifestyle represents the factor that have a major impact in its development.…”

Section: Discussionmentioning

confidence: 99%

The beneficial effects of physical activity and weight loss on human colorectal carcinoma cell lines

Polito¹,

Scarinci²,

Ambrosi³

et al. 2020

Journal of Human Sport and Exercise - 2020 - Winter Conferences of Sports Science

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Recent studies have demonstrated that obesity is a significant risk factor for the development of several malignancies such as cancer. Colorectal cancer is among the most common cancers worldwide and is strong linked to obesity. A healthy lifestyle, characterized by hypocaloric diet and physical activity, is important to reduce a chronic inflammation, oxidative stress and metabolic disorders typical of obesity (Messina et al, 2018; Messina et al, 2017; Messina et al, 2015). It is well known that the chronic inflammation state and oxidative stress are responsible for the aging and development of many diseases, such as cancer. Dysregulation of cytokine's secretion probably participates in the establishment of cancer in obese patients. The aim of this study is to analyse the effects of sera from obese patients subjected to a physical activity program before and after weight loss on cell viability, apoptosis and oxidative stress in HCT116 carcinoma cell line treated for 24, 48 and 72 hours through MTT test. We analysed the expression of cytokines in HCT116 cells. We found that sera from obese after physical activity intervention compared to treatment with sera from obese patients before physical activity intervention reduce the survival rate of HCT116 cells through induction of apoptosis and oxidative stress. Finally, we found a reduction of mRNA levels corresponding to the pro-inflammatory IL-6 and IL-8 cytokines together with an increase of the anti-inflammatory IL-10 cytokine. We can conclude that the physical activity has numerous beneficial effects also in colorectal cancer cell, indeed the physical activity and weight loss in obese subjects have an inhibitory and anti-inflammatory effects in a short period on carcinoma cell line.

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Simultaneous Activation of Mu and Delta Opioid Receptors Reduces Allodynia and Astrocytic Connexin 43 in an Animal Model of Neuropathic Pain

Cited by 45 publications

References 70 publications

The Role of Inflammation and Inflammasome in Myeloproliferative Disease

The Role of Inflammation and Inflammasome in Myeloproliferative Disease

Inhibition of TLR4 Signaling Affects Mitochondrial Fitness and Overcomes Bortezomib Resistance in Myeloma Plasma Cells

The beneficial effects of physical activity and weight loss on human colorectal carcinoma cell lines

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