Role of interleukin-1 in stress responses

: Chronic inflammation can lead to the development of many diseases including cancer. Inflammatory bowel disease (IBD) that includes both ulcerative colitis (UC) and Crohn's disease (CD) are risk factors for the development of colorectal cancer (CRC). Many cytokines produced primarily by the gut immune cells either during or in response to localized inflammation in the colon and rectum are known to stimulate the complex interactions between the different cell types in the gut environment resulting in acute inflammation. Subsequently, chronic inflammation together with genetic and epigenetic changes has been shown to lead to the development and progression of CRC. Various cell types present in the colon such as enterocytes, Paneth cells, goblet cells and macrophages express receptors for inflammatory cytokines and respond to tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6 and other cytokines. Among the several cytokines produced, TNF-α and IL-1β are the key proinflammatory molecules that play critical roles in the development of CRC. The current review is intended to consolidate the published findings to focus on the role of proinflammatory cytokines, namely TNF-α and IL-1β, on inflammation (and the altered immune response) in the gut, to better understand the development of CRC in IBD, using various experimental model systems, preclinical and clinical studies. Moreover, this review also highlights the current therapeutic strategies available (monotherapy and combination therapy), to alleviate the symptoms or treat inflammationassociated CRC by using monoclonal antibodies or aptamers to block proinflammatory molecules, inhibitors of tyrosine kinases in inflammatory signaling cascade, competitive inhibitors of proinflammatory molecules, and the nucleic acid drugs like small activating RNAs (saRNAs) or microRNA (miRNA) mimics to activate tumor suppressor or repress oncogene/proinflammatory cytokine gene expression.

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Flavonoids: Potential Candidates for the Treatment of Neurodegenerative Disorders

Biomedicines ◽

10.3390/biomedicines9020099 ◽

2021 ◽

Vol 9 (2) ◽

pp. 99

Author(s):

Shweta Devi ◽

Vijay Kumar ◽

Sandeep Kumar Singh ◽

Ashish Kant Dubey ◽

Jong-Joo Kim

Keyword(s):

Stress Response ◽

Stress Responses ◽

Neurodegenerative Disorders ◽

Cell Damage ◽

Cellular Stress ◽

Clinical Manifestations ◽

Cellular Stress Response ◽

Dramatic Rise ◽

Cellular Stress Responses

Neurodegenerative disorders, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), Amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD), are the most concerning disorders due to the lack of effective therapy and dramatic rise in affected cases. Although these disorders have diverse clinical manifestations, they all share a common cellular stress response. These cellular stress responses including neuroinflammation, oxidative stress, proteotoxicity, and endoplasmic reticulum (ER)-stress, which combats with stress conditions. Environmental stress/toxicity weakened the cellular stress response which results in cell damage. Small molecules, such as flavonoids, could reduce cellular stress and have gained much attention in recent years. Evidence has shown the potential use of flavonoids in several ways, such as antioxidants, anti-inflammatory, and anti-apoptotic, yet their mechanism is still elusive. This review provides an insight into the potential role of flavonoids against cellular stress response that prevent the pathogenesis of neurodegenerative disorders.

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Mitochondrial Sirtuins in Reproduction

Antioxidants ◽

10.3390/antiox10071047 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1047

Author(s):

Giovanna Di Emidio ◽

Stefano Falone ◽

Paolo Giovanni Artini ◽

Fernanda Amicarelli ◽

Anna Maria D’Alessandro ◽

...

Keyword(s):

Stress Responses ◽

Metabolic Pathways ◽

Redox Balance ◽

Antioxidant Defenses ◽

Metabolic Abnormalities ◽

Female Reproduction ◽

Mitochondrial Dysfunctions ◽

Early Embryos ◽

The Relationship

Mitochondria act as hubs of numerous metabolic pathways. Mitochondrial dysfunctions contribute to altering the redox balance and predispose to aging and metabolic alterations. The sirtuin family is composed of seven members and three of them, SIRT3-5, are housed in mitochondria. They catalyze NAD+-dependent deacylation and the ADP-ribosylation of mitochondrial proteins, thereby modulating gene expression and activities of enzymes involved in oxidative metabolism and stress responses. In this context, mitochondrial sirtuins (mtSIRTs) act in synergistic or antagonistic manners to protect from aging and aging-related metabolic abnormalities. In this review, we focus on the role of mtSIRTs in the biological competence of reproductive cells, organs, and embryos. Most studies are focused on SIRT3 in female reproduction, providing evidence that SIRT3 improves the competence of oocytes in humans and animal models. Moreover, SIRT3 protects oocytes, early embryos, and ovaries against stress conditions. The relationship between derangement of SIRT3 signaling and the imbalance of ROS and antioxidant defenses in testes has also been demonstrated. Very little is known about SIRT4 and SIRT5 functions in the reproductive system. The final goal of this work is to understand whether sirtuin-based signaling may be taken into account as potential targets for therapeutic applications in female and male infertility.

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Loss of mGluR5 in D1 Receptor-Expressing Neurons Improves Stress Coping

International Journal of Molecular Sciences ◽

10.3390/ijms22157826 ◽

2021 ◽

Vol 22 (15) ◽

pp. 7826

Author(s):

Luca Zangrandi ◽

Claudia Schmuckermair ◽

Hussein Ghareh ◽

Federico Castaldi ◽

Regine Heilbronn ◽

...

Keyword(s):

Stress Responses ◽

Metabotropic Glutamate Receptor ◽

Forced Swim Test ◽

Functional Integration ◽

D1 Receptor ◽

Conditional Knockout ◽

Stress Coping ◽

Metabotropic Glutamate ◽

Internal States

The metabotropic glutamate receptor type 5 (mGluR5) has been proposed to play a crucial role in the selection and regulation of cognitive, affective, and emotional behaviors. However, the mechanisms by which these receptors mediate these effects remain largely unexplored. Here, we studied the role of mGluR5 located in D1 receptor-expressing (D1) neurons in the manifestation of different behavioral expressions. Mice with conditional knockout (cKO) of mGluR5 in D1 neurons (mGluR5D1 cKO) and littermate controls displayed similar phenotypical profiles in relation to memory expression, anxiety, and social behaviors. However, mGluR5D1 cKO mice presented different coping mechanisms in response to acute escapable or inescapable stress. mGluR5D1 cKO mice adopted an enhanced active stress coping strategy upon exposure to escapable stress in the two-way active avoidance (TWA) task and a greater passive strategy upon exposure to inescapable stress in the forced swim test (FST). In summary, this work provides evidence for a functional integration of the dopaminergic and glutamatergic system to mediate control over internal states upon stress exposure and directly implicates D1 neurons and mGluR5 as crucial mediators of behavioral stress responses.

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Interleukin-1 beta-induced formation of EPR-detectable iron-nitrosyl complexes in islets of Langerhans. Role of nitric oxide in interleukin-1 beta-induced inhibition of insulin secretion.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)54642-1 ◽

1991 ◽

Vol 266 (32) ◽

pp. 21351-21354

Author(s):

J.A. Corbett ◽

J.R. Lancaster ◽

M.A. Sweetland ◽

M.L. McDaniel

Keyword(s):

Nitric Oxide ◽

Insulin Secretion ◽

Islets Of Langerhans ◽

Interleukin 1 ◽

Interleukin 1 Beta ◽

Nitrosyl Complexes ◽

Iron Nitrosyl ◽

Iron Nitrosyl Complexes

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The Potential Role of IL1RAP on Tumor Microenvironment-Related Inflammatory Factors in Stomach Adenocarcinoma

Technology in Cancer Research & Treatment ◽

10.1177/1533033821995282 ◽

2021 ◽

Vol 20 ◽

pp. 153303382199528

Author(s):

Qing Lv ◽

Qinghua Xia ◽

Anshu Li ◽

Zhiyong Wang

Keyword(s):

Tumor Microenvironment ◽

Interleukin 1 ◽

Mrna Level ◽

Inflammatory Factors ◽

Stomach Carcinoma ◽

Downstream Target ◽

Volume Weight

This study was performed to investigate the role of interleukin-1 receptor accessory protein (IL1RAP) in stomach carcinoma in vitro and in vivo, determine whether IL1RAP knockdown could regulate the development of stomach carcinoma, and elucidate the relationship between IL1RAP knockdown and inflammation by tumor microenvironment-related inflammatory factors in stomach carcinoma. We first used TCGA and GEPIA systems to predict the potential function of IL1RAP. Second, western blot and RT-PCR were used to analyze the expression, or mRNA level, of IL1RAP at different tissue or cell lines. Third, the occurrence and development of stomach carcinoma in vitro and in vivo were observed by using IL1RAP knockdown lentivirus. Finally, the inflammation of stomach carcinoma in vitro and in vivo was observed. Results show that in GEPIA and TCGA systems, IL1RAP expression in STAD tumor tissue was higher than normal, and high expression of IL1RAP in STAD patients had a worse prognostic outcome. Besides, GSEA shown IL1RAP was negative correlation of apopopsis, TLR4 and NF-κB signaling pathway. We also predicted that IL1RAP may related to IL-1 s, IL-33, and IL-36 s in STAD. The IL1RAP expression and mRNA level in tumor, or MGC803, cells were increased. Furthermore, IL1RAP knockdown by lentivirus could inhibit stomach carcinoma development in vitro and in vivo through weakening tumor cell proliferation, migration, invasion, therefore reducing tumor volume, weight, and biomarker levels, and increasing apoptotic level. Finally, we found IL1RAP knockdown could increase inflammation of tumor microenvironment-related inflammatory factors of stomach carcinoma, in vitro and in vivo. Our study demonstrates that IL1RAP is possibly able to regulate inflammation and apoptosis in stomach carcinoma. Furthermore, TLR4, NF-κB, IL-1 s, IL-33, and IL-36 s maybe the downstream target factor of IL1RAP in inflammation. These results may provide a new strategy for stomach carcinoma development by regulating inflammation.

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Possible Role of Peroxynitrite in the Responses Induced by Fusicoccin in Plant Cultured Cells

Plants ◽

10.3390/plants10010182 ◽

2021 ◽

Vol 10 (1) ◽

pp. 182 ◽

Cited By ~ 1

Author(s):

Massimo Malerba ◽

Raffaella Cerana

Keyword(s):

Cytochrome C ◽

Dna Fragmentation ◽

Stress Responses ◽

Molecular Chaperones ◽

Caspase 3 ◽

Cultured Cells ◽

Acer Pseudoplatanus ◽

Cytochrome C Release ◽

Induced Stress

Fusicoccin (FC) is a well-known phytotoxin able to induce in Acer pseudoplatanus L. (sycamore) cultured cells, a set of responses similar to those induced by stress conditions. In this work, the possible involvement of peroxynitrite (ONOO−) in FC-induced stress responses was studied measuring both in the presence and in the absence of 2,6,8-trihydroxypurine (urate), a specific ONOO− scavenger: (1) cell death; (2) specific DNA fragmentation; (3) lipid peroxidation; (4) production of RNS and ROS; (5) activity of caspase-3-like proteases; and (6) release of cytochrome c from mitochondria, variations in the levels of molecular chaperones Hsp90 in the mitochondria and Hsp70 BiP in the endoplasmic reticulum (ER), and of regulatory 14-3-3 proteins in the cytosol. The obtained results indicate a role for ONOO− in the FC-induced responses. In particular, ONOO− seems involved in a PCD form showing apoptotic features such as specific DNA fragmentation, caspase-3-like protease activity, and cytochrome c release from mitochondria.

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