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Nature Genetics Jan 2024Inflammation is characterized by a biphasic cycle consisting initially of a proinflammatory phase that is subsequently resolved by anti-inflammatory processes....
Inflammation is characterized by a biphasic cycle consisting initially of a proinflammatory phase that is subsequently resolved by anti-inflammatory processes. Interleukin-1β (IL-1β) is a master regulator of proinflammation and is encoded within the same topologically associating domain (TAD) as IL-37, which is an anti-inflammatory cytokine that opposes the function of IL-1β. Within this TAD, we identified a long noncoding RNA called AMANZI, which negatively regulates IL-1β expression and trained immunity through the induction of IL37 transcription. We found that the activation of IL37 occurs through the formation of a dynamic long-range chromatin contact that leads to the temporal delay of anti-inflammatory responses. The common variant rs16944 present in AMANZI augments this regulatory circuit, predisposing individuals to enhanced proinflammation or immunosuppression. Our work illuminates a chromatin-mediated biphasic circuit coordinating expression of IL-1β and IL-37, thereby regulating two functionally opposed states of inflammation from within a single TAD.
Topics: Humans; Interleukin-1beta; Chromatin; Inflammation; Cytokines; Anti-Inflammatory Agents; Interleukin-1
PubMed: 38092881
DOI: 10.1038/s41588-023-01598-2 -
Hypertension (Dallas, Tex. : 1979) Feb 2020
Topics: Blood Pressure; Blood Pressure Determination; Humans; Hypertension; Inflammation; Interleukin-1beta
PubMed: 31884858
DOI: 10.1161/HYPERTENSIONAHA.119.14195 -
Journal of Hematology & Oncology Mar 2023Inflammasomes are macromolecular platforms formed in response to damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns, whose formation... (Review)
Review
Inflammasomes are macromolecular platforms formed in response to damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns, whose formation would cause maturation of interleukin-1 (IL-1) family members and gasdermin D (GSDMD), leading to IL-1 secretion and pyroptosis respectively. Several kinds of inflammasomes detecting different types of dangers have been found. The activation of inflammasomes is regulated at both transcription and posttranscription levels, which is crucial in protecting the host from infections and sterile insults. Present findings have illustrated that inflammasomes are involved in not only infection but also the pathology of tumors implying an important link between inflammation and tumor development. Generally, inflammasomes participate in tumorigenesis, cell death, metastasis, immune evasion, chemotherapy, target therapy, and radiotherapy. Inflammasome components are upregulated in some tumors, and inflammasomes can be activated in cancer cells and other stromal cells by DAMPs, chemotherapy agents, and radiation. In some cases, inflammasomes inhibit tumor progression by initiating GSDMD-mediated pyroptosis in cancer cells and stimulating IL-1 signal-mediated anti-tumor immunity. However, IL-1 signal recruits immunosuppressive cell subsets in other cases. We discuss the conflicting results and propose some possible explanations. Additionally, we also summarize interventions targeting inflammasome pathways in both preclinical and clinical stages. Interventions targeting inflammasomes are promising for immunotherapy and combination therapy.
Topics: Humans; Inflammasomes; Tumor Microenvironment; Interleukin-1; Inflammation
PubMed: 36932407
DOI: 10.1186/s13045-023-01407-7 -
Frontiers in Immunology 2023Clinical studies have suggested a bidirectional association between non-alcoholic steatohepatitis (NASH) and psoriasis, affecting each other's development and severity....
INTRODUCTION
Clinical studies have suggested a bidirectional association between non-alcoholic steatohepatitis (NASH) and psoriasis, affecting each other's development and severity. Here, we explored bidirectional causal linkages between NASH and psoriasis using a murine model.
METHODS
NASH was induced in mice by streptozotocin injection at 2 days of age and by high-fat diet feeding (STAM™ model). Psoriasis was induced by topical application of imiquimod (IMQ) on the ear. The severities of liver damage and psoriatic skin changes were determined using histological analysis. Gene expression in the skin tissues was evaluated using quantitative PCR analysis. Serum cytokine levels were determined using enzyme-linked immunosorbent assay. To examine the innate immune responses of normal human epidermal keratinocytes (NHEKs), the cells were treated with interleukin (IL)-17A, tumor necrosis factor (TNF)-α, and AdipoRon, an adiponectin receptor agonist.
RESULTS AND DISCUSSION
There were no differences in the degree of liver tissue damage (fat deposition, inflammation, and fibrosis) between NASH mice with and those without psoriasis. Conversely, the co-occurrence of NASH significantly augmented psoriatic skin changes, represented by epidermal hyperplasia, in psoriatic mice. Pro-inflammatory cytokines were expressed in the inflamed skin of psoriatic mice, and the expression of genes, especially , , , and , was significantly upregulated by the co-occurrence of NASH. The expression of keratinocyte activation marker genes and was also upregulated by the co-occurrence of NASH. The serum TNF-α and IL-17 levels were increased by the co-occurrence of NASH and psoriasis. The serum adiponectin levels decreased in NASH mice compared with that in non-NASH mice. In NHEK culture, TNF-α and IL-17A synergistically upregulated , , and expression. The upregulated pro-inflammatory gene expression was suppressed by AdipoRon treatment, reflecting the anti-inflammatory capacity of adiponectin.
CONCLUSION
The co-occurrence of NASH exacerbated psoriatic skin changes associated with increased serum inflammatory cytokine levels and decreased serum adiponectin levels. Combined with findings, increased inflammatory cytokine levels and decreased adiponectin levels likely promote innate immune responses in epidermal keratinocytes in psoriatic skin lesions. Overall, therapeutic intervention for co-occurring NASH is essential to achieve a favorable prognosis of psoriasis in clinical practice.
Topics: Humans; Mice; Animals; Adiponectin; Tumor Necrosis Factor-alpha; Disease Models, Animal; Psoriasis; Non-alcoholic Fatty Liver Disease; Cytokines; Interleukin-1
PubMed: 37646025
DOI: 10.3389/fimmu.2023.1214623 -
Biochemical Society Transactions Feb 2022Interleukin (IL)-36 is a subfamily, of the IL-1 super-family and includes IL-36α, IL-36β, IL-36γ, IL-38 and IL-36Ra. IL-36 cytokines are involved in the pathology of... (Review)
Review
Interleukin (IL)-36 is a subfamily, of the IL-1 super-family and includes IL-36α, IL-36β, IL-36γ, IL-38 and IL-36Ra. IL-36 cytokines are involved in the pathology of multiple tissues, including skin, lung, oral cavity, intestine, kidneys and joints. Recent studies suggest that IL-36 signaling regulates autoimmune disease in addition to antibacterial and antiviral responses. Most research has focused on IL-36 in skin diseases such as psoriasis, however, studies on intestinal diseases are also underway. This review outlines what is known about the bioactivity of the IL-36 subfamily and its role in the pathogenesis of intestinal diseases such as inflammatory bowel disease, colorectal cancer, gut dysbacteriosis and infection, and proposes that IL-36 may be a target for novel therapeutic strategies to prevent or treat intestinal diseases.
Topics: Cytokines; Humans; Interleukin-1; Interleukins; Intestinal Diseases; Psoriasis
PubMed: 35166319
DOI: 10.1042/BST20211264 -
Experimental Physiology Jul 2023What is the topic of this review? This review focuses on the physiological role of the cytokine interleukin-1β in the CNS. What advances does it highlight?... (Review)
Review
NEW FINDINGS
What is the topic of this review? This review focuses on the physiological role of the cytokine interleukin-1β in the CNS. What advances does it highlight? Traditionally, interleukin-1β is known as a key mediator of inflammation and immunity. This review highlights the more recent findings describing how interleukin-1β signalling is required to maintain homeostasis in the CNS.
ABSTRACT
Since its discovery in the early 1940s, the interleukin-1 (IL-1) cytokine family has been associated primarily with acute and chronic inflammation. The family member IL-1β is produced by different leucocytes, endothelial cells and epithelial cells. This cytokine has been characterized as a key modulator of inflammation and innate immunity because it induces the transcription of several downstream inflammatory genes. More recently, several groups have demonstrated that IL-1β production is also required to maintain homeostasis in several organ systems. This review focuses on providing an overview of the more recently characterized role of IL-1β in the physiology of the CNS. So far, IL-1β signalling has been implicated in neuronal survival, neurite growth, synaptic pruning, synaptic transmission, neuroplasticity and neuroendocrine functions.
Topics: Humans; Cytokines; Endothelial Cells; Inflammation; Inflammation Mediators; Interleukin-1beta; Neurophysiology
PubMed: 37031383
DOI: 10.1113/EP090780 -
International Journal of Molecular... Jan 2024With cardiovascular disease (CVD) being a primary source of global morbidity and mortality, it is crucial that we understand the molecular pathophysiological mechanisms... (Review)
Review
With cardiovascular disease (CVD) being a primary source of global morbidity and mortality, it is crucial that we understand the molecular pathophysiological mechanisms at play. Recently, numerous pro-inflammatory cytokines have been linked to several different CVDs, which are now often considered an adversely pro-inflammatory state. These cytokines most notably include interleukin-6 (IL-6),tumor necrosis factor (TNF)α, and the interleukin-1 (IL-1) family, amongst others. Not only does inflammation have intricate and complex interactions with pathophysiological processes such as oxidative stress and calcium mishandling, but it also plays a role in the balance between tissue repair and destruction. In this regard, pre-clinical and clinical evidence has clearly demonstrated the involvement and dynamic nature of pro-inflammatory cytokines in many heart conditions; however, the clinical utility of the findings so far remains unclear. Whether these cytokines can serve as markers or risk predictors of disease states or act as potential therapeutic targets, further extensive research is needed to fully understand the complex network of interactions that these molecules encompass in the context of heart disease. This review will highlight the significant advances in our understanding of the contributions of pro-inflammatory cytokines in CVDs, including ischemic heart disease (atherosclerosis, thrombosis, acute myocardial infarction, and ischemia-reperfusion injury), cardiac remodeling (hypertension, cardiac hypertrophy, cardiac fibrosis, cardiac apoptosis, and heart failure), different cardiomyopathies as well as ventricular arrhythmias and atrial fibrillation. In addition, this article is focused on discussing the shortcomings in both pathological and therapeutic aspects of pro-inflammatory cytokines in CVD that still need to be addressed by future studies.
Topics: Humans; Cardiovascular Diseases; Cytokines; Heart Diseases; Interleukin-1; Heart Failure; Tumor Necrosis Factor-alpha
PubMed: 38256155
DOI: 10.3390/ijms25021082 -
Cytokine Jun 2022The interleukin-1 (IL-1) family of cytokines and receptors are implicated in the functioning of innate and adaptive immunity and the genesis of inflammation. They are... (Review)
Review
The interleukin-1 (IL-1) family of cytokines and receptors are implicated in the functioning of innate and adaptive immunity and the genesis of inflammation. They are widely expressed in structural and immune cells with marked expression within barrier mucosal surfaces. In the lung, gut and skin, which are common entry sites for pathogens, they play essential functions in maintaining the functional integrity of the barrier and manage innate and adaptive immunity in response to insult and infections. In tissue sites, the IL-1 cytokines are tightly regulated by mechanisms involving decoy receptors and protease degradation. Dysregulation of these processes are associated with aberrant tissue inflammation leading to a number of inflammatory diseases. This review will address the roles of the different IL-1 cytokines at the lung, gut and skin barrier surfaces at homeostasis, and their roles as inflammatory mediators in diseases such as asthma, chronic obstructive pulmonary disease, inflammatory bowel diseases, atopic dermatitis and psoriasis.
Topics: Adaptive Immunity; Cytokines; Humans; Immunity, Innate; Inflammation; Inflammatory Bowel Diseases; Interleukin-1
PubMed: 35462264
DOI: 10.1016/j.cyto.2022.155890 -
Journal of Food Biochemistry May 2021The immune system plays an important role in cancer development, but some tumor cells can evade or inhibit the processes of innate and adaptive immunity. This review... (Review)
Review
The immune system plays an important role in cancer development, but some tumor cells can evade or inhibit the processes of innate and adaptive immunity. This review made a description of honey and its proteins effect on diverse mediators from the immune system. Scientific evidence reported that many types of honey (jungle, manuka, pasture, and others) and some isolated proteins enhanced the release of reactive oxygen species (O and H O ) and cytokines (mostly IL-1β, IL-6, and TNF-α) by innate immune system cells. Furthermore, honey elicited proliferation and functions of T lymphocytes, cells related to specific adaptive immune responses. These studies have established a precedent over the honey and its properties on the immune system, demonstrating that it can promote the innate and adaptive immunity. PRACTICAL APPLICATIONS: Cancer is a genetic illness that represents a world health problem. Recognizing the potential of diet therapy in the prevention and treatment of chronic diseases, the present work summarizes the effects of honey on the immune system and mediators involved in cancer elimination processes, establishing the importance of this natural product as a future anticancer agent.
Topics: Cytokines; Honey; Humans; Neoplasms; Reactive Oxygen Species; Tumor Necrosis Factor-alpha
PubMed: 33768550
DOI: 10.1111/jfbc.13613 -
Inflammopharmacology Aug 2023Burn management is a natural and distinctly programmed process involving overlapping phases of hemostasis, inflammation, proliferation and remodeling. Burn wound healing... (Review)
Review
Burn management is a natural and distinctly programmed process involving overlapping phases of hemostasis, inflammation, proliferation and remodeling. Burn wound healing involves initiation of inflammation, re-epithelialization, granulation, neovascularization and wound contraction. Despite the availability of multiple preparations for management of burn wound, there is dire need for efficacious alternative agents. Current approaches for burn wound management include pharmaceutical agents and antibiotics. However, high cost of synthetic drugs and accelerated resistance to antibiotics is challenging for both developed and developing nations. Among alternative options, medicinal plants have been a biocompatible, safe and affordable source of preventive/curative approaches. Due to cultural acceptance and patient compliance, there has been a focus on the use of botanical drugs and phytochemicals for burn wound healing. Keeping in consideration of medicinal herbs and phytochemicals as suitable therapeutic/adjuvant agents for burn wound management, this review highlights therapeutic potential of 35 medicinal herbs and 10 phytochemicals. Among these, Elaeis guineensis, Ephedra ciliate and Terminalia avicennioides showed better burn wound healing potential with varied mechanisms such as modulation of TNF-alpha, inflammatory cytokines, nitric oxide, eicosanoids, ROS and leukocyte response. Phytochemicals (oleanolic acid, ursolic acid, kirenol) also showed promising role in burn wound management though various pathways involving such as down regulation of TNF-alpha, IL-6 and inflammatory mediators including plasma proteases and arachidonic acid metabolites. This review provides a pavement for therapeutic/adjuvant use of potential botanical drugs and novel druggable phyto-compounds to target skin burn injury with diverse mechanisms, affordability and safety profile.
Topics: Humans; Plants, Medicinal; Tumor Necrosis Factor-alpha; Wound Healing; Inflammation; Phytochemicals
PubMed: 37204694
DOI: 10.1007/s10787-023-01246-5