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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 -
Clinica Chimica Acta; International... Oct 2015Intervertebral disk degeneration (IDD) is the most common diagnosis in patients with low back pain, a main cause of musculoskeletal disability in the world.... (Review)
Review
Intervertebral disk degeneration (IDD) is the most common diagnosis in patients with low back pain, a main cause of musculoskeletal disability in the world. Interleukin-1 (IL-1) β is the most important member of the IL-1 family, and has a strong pro-inflammatory activity by stimulating the secretion of multiple pro-inflammatory mediators. IL-1β is highly expressed in degenerative intervertebral disk (IVD) tissues and cells, and it has been shown to be involved in multiple pathological processes during disk degeneration, including inflammatory responses, matrix destruction, angiogenesis and innervation, cellular apoptosis, oxidative stress and cellular senescence. However, inhibition of IL-1β is found to promote extracellular matrix (ECM) repair and protect against disk regeneration. In this review, after a brief description of IL-1β signaling, we mainly focus on the expression profiles, roles and therapeutic potential of IL-1β in IDD. A better understanding will help develop novel IL-1β-based therapeutic interventions for degenerative disk disease.
Topics: Animals; Gene Expression Regulation; Humans; Interleukin-1beta; Intervertebral Disc Degeneration; Molecular Targeted Therapy; Signal Transduction
PubMed: 26341894
DOI: 10.1016/j.cca.2015.08.029 -
Sleep Medicine Reviews Aug 2018This review details tumor necrosis factor alpha (TNF) biology and its role in sleep, and describes how TNF medications influence sleep/wake activity. Substantial... (Review)
Review
This review details tumor necrosis factor alpha (TNF) biology and its role in sleep, and describes how TNF medications influence sleep/wake activity. Substantial evidence from healthy young animals indicates acute enhancement or inhibition of endogenous brain TNF respectively promotes and inhibits sleep. In contrast, the role of TNF in sleep in most human studies involves pathological conditions associated with chronic elevations of systemic TNF and disrupted sleep. Normalization of TNF levels in such patients improves sleep. A few studies involving normal healthy humans and their TNF levels and sleep are consistent with the animal studies but are necessarily more limited in scope. TNF can act on established sleep regulatory circuits to promote sleep and on the cortex within small networks, such as cortical columns, to induce sleep-like states. TNF affects multiple synaptic functions, e.g., its role in synaptic scaling is firmly established. The TNF-plasticity actions, like its role in sleep, can be local network events suggesting that sleep and plasticity share biochemical regulatory mechanisms and thus may be inseparable from each other. We conclude that TNF is involved in sleep regulation acting within an extensive tightly orchestrated biochemical network to niche-adapt sleep in health and disease.
Topics: Animals; Brain; Humans; Neuronal Plasticity; Sleep; Tumor Necrosis Factor-alpha
PubMed: 29153862
DOI: 10.1016/j.smrv.2017.10.005 -
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 -
Current Pharmaceutical Design 2015Rheumatoid arthritis (RA) is a chronic inflammatory disease that involves synovial tissue and leads to joint destruction. There are currently 5 tumor necrosis factor... (Review)
Review
Rheumatoid arthritis (RA) is a chronic inflammatory disease that involves synovial tissue and leads to joint destruction. There are currently 5 tumor necrosis factor (TNF) antagonists licensed for the treatment of RA. This review summarizes the predictors of response to TNF antagonists in RA. Demographic variables were found to predict response, although not consistently. The variables associated with poor clinical response were presence of radiographic joint erosions at baseline, poor functional capacity at baseline, presence of human antibodies against TNF chimeric antibodies, and increase in anti-DNA and antinuclear antibodies. In selected populations, polymorphisms of TNF, TNF receptor, and Fc γ receptor were related to clinical response. Expression of TNF and other inflammatory cytokines in synovial tissue was explored. The heterogeneity of study populations limits the generalizability of the results in most studies.
Topics: Arthritis, Rheumatoid; Humans; Tumor Necrosis Factor-alpha
PubMed: 25163737
DOI: 10.2174/1381612820666140825124152 -
Clinica Chimica Acta; International... Jan 2021Rheumatoid arthritis (RA) is a serious disorder of the joints affecting 1 or 2% of the population aged between 20 and 50 years worldwide. RA is the foremost cause of... (Review)
Review
Rheumatoid arthritis (RA) is a serious disorder of the joints affecting 1 or 2% of the population aged between 20 and 50 years worldwide. RA is the foremost cause of disability in developing and Western populations. It is an autoimmune disease-causing inflammation and pain involving synovial joints. Pro-inflammatory markers, including cytokines, such as interleukin -1 (IL-1), IL-6, IL-7, IL-8, and tumor necrosis factor-α (TNF-α) are involved in RA. RA treatment involves TNF-α blockade, B cell therapy, IL-1 and IL-6 blockade, and angiogenesis inhibition. Synthetic drugs available for the treatment of RA include disease-modifying anti-rheumatic drugs (DMARD), such as cyclophosphamide, sulfasalazine, methotrexate, nonsteroidal anti-inflammatory drugs (NSAIDs), and intramuscular gold. These agents induce adverse hepatorenal effects, hypertension, and gastric ulcers. We found that patients diagnosed with chronic pain, as in RA, and those refractory to contemporary management are most likely to seek traditional medicine. Approximately 60-90% of patients with arthritis use traditional medicines. Therefore, the efficacy and safety of these traditional medicines need to be established. The treatment for RA entails a comprehensive multidisciplinary strategy to reduce pain and inflammation and to restore the activity of joints. The potential medicinal plants exhibiting anti-arthritic and anti-rheumatic pharmacological activity are reviewed here.
Topics: Adult; Antirheumatic Agents; Arthritis, Rheumatoid; Humans; Interleukin-1; Methotrexate; Middle Aged; Tumor Necrosis Factor-alpha; Young Adult
PubMed: 33186593
DOI: 10.1016/j.cca.2020.11.003 -
Frontiers in Immunology 2020The role of inflammation in atherosclerosis has been recognized several decades ago and existing treatments provide benefits in part through non-specific... (Review)
Review
The role of inflammation in atherosclerosis has been recognized several decades ago and existing treatments provide benefits in part through non-specific anti-inflammatory actions. Compared with other cytokines, interleukin-1β (IL-1β) is associated with acute and chronic inflammation. Anti-inflammatory therapy with canakinumab targeting the IL-1β innate immunity pathway could significantly reduce the rate of recurrent cardiovascular events than placebo. The results of CANTOS suggested an important role of IL-1β in atherosclerosis. However, there are numerous mechanisms that are to be clarified. We herein discussed the important immunomodulatory effect IL-1β exerts on atherosclerosis and the potential mechanisms underlying it. We also reviewed bench-to-bedside clinical translation of IL-1β neutralizing strategies associated with the use of IL-1β blockade in patients with atherosclerosis.
Topics: Animals; Atherosclerosis; Humans; Interleukin-1alpha; Interleukin-1beta
PubMed: 33362770
DOI: 10.3389/fimmu.2020.589654 -
Cells Jan 2021Interleukin-1α (IL-1α) is a major alarmin cytokine which triggers and boosts the inflammatory responses. Since its discovery in the 1940s, the structure and... (Review)
Review
Interleukin-1α (IL-1α) is a major alarmin cytokine which triggers and boosts the inflammatory responses. Since its discovery in the 1940s, the structure and bioactivity of IL-1α has been extensively studied and emerged as a vital regulator in inflammation and hematopoiesis. IL-1α is translated as a pro-form with minor bioactivity. The pro-IL-1α can be cleaved by several proteases to generate the N terminal and C terminal form of IL-1α. The C terminal form of IL-1α (mature form) has several folds higher bioactivity compared with its pro-form. IL-1α is a unique cytokine which could localize in the cytosol, membrane, nucleus, as well as being secreted out of the cell. However, the processing mechanism and physiological significance of these differentially localized IL-1α are still largely unknown. Accumulating evidence suggests IL-1α is involved in cancer pathogenesis. The role of IL-1α in cancer development is controversial as it exerts both pro- and anti-tumor roles in different cancer types. Here, we review the recent development in the processing and signaling of IL-1α and summarize the functions of IL-1α in cancer development.
Topics: Animals; Carcinogenesis; Disease Progression; Humans; Interleukin-1alpha; Neoplasms; Protein Processing, Post-Translational; Signal Transduction
PubMed: 33430381
DOI: 10.3390/cells10010092 -
Journal of the American Society of... Sep 2016Kidney injury implies danger signaling and a response by the immune system. The inflammasome is a central danger recognition platform that triggers local and systemic... (Review)
Review
Kidney injury implies danger signaling and a response by the immune system. The inflammasome is a central danger recognition platform that triggers local and systemic inflammation. In immune cells, inflammasome activation causes the release of mature IL-1β and of the alarmin IL-1α Dying cells release IL-1α also, independently of the inflammasome. Both IL-1α and IL-1β ligate the same IL-1 receptor (IL-1R) that is present on nearly all cells inside and outside the kidney, further amplifying cytokine and chemokine release. Thus, the inflammasome-IL-1α/IL-β-IL-1R system is a central element of kidney inflammation and the systemic consequences. Seminal discoveries of recent years have expanded this central paradigm of inflammation. This review gives an overview of arising concepts of inflammasome and IL-1α/β regulation in renal cells and in experimental kidney disease models. There is a pipeline of compounds that can interfere with the inflammasome-IL-1α/IL-β-IL-1R system, ranging from recently described small molecule inhibitors of NLRP3, a component of the inflammasome complex, to regulatory agency-approved IL-1-neutralizing biologic drugs. Based on strong theoretic and experimental rationale, the potential therapeutic benefits of using such compounds to block the inflammasome-IL-1α/IL-β-IL-1R system in kidney disease should be further explored.
Topics: Alarmins; Animals; Disease Models, Animal; Humans; Inflammasomes; Interleukin-1alpha; Interleukin-1beta; Kidney Diseases
PubMed: 27516236
DOI: 10.1681/ASN.2016020177 -
Journal of Asian Natural Products... Jun 2023Two new sesquiterpenoids, named 9,10-dihydroxy-albaflavenone () and 5-hydroxy-albaflavenone () were isolated from . Their structures and absolute configurations were...
Two new sesquiterpenoids, named 9,10-dihydroxy-albaflavenone () and 5-hydroxy-albaflavenone () were isolated from . Their structures and absolute configurations were determined by NMR, ECD and HRESIMS. Compounds and showed anti-inflammatory activity by inhibiting TNF- and NO secretion to varying degrees.
Topics: Basidiomycota; Sesquiterpenes; Tumor Necrosis Factor-alpha
PubMed: 35929891
DOI: 10.1080/10286020.2022.2106223