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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 -
Journal of Cellular and Molecular... Dec 2023Tumour necrosis factor-α (TNF-α) is a cytokine involved in systemic inflammation. TNF-α slows down osteogenic differentiation, which may contribute to poor bone...
Tumour necrosis factor-α (TNF-α) is a cytokine involved in systemic inflammation. TNF-α slows down osteogenic differentiation, which may contribute to poor bone development in the inflammatory microenvironment. TNF-α inhibits osteogenic differentiation by activating the JAK-STAT3 pathway, of which Signal transducer and activator of transcription 3 (STAT3)-interacting protein 1 (StIP1, also known as elongator complex protein 2, ELP2) is a key protein in the JAK-STAT3 pathway. We investigated whether and how ELP2 activation mediates the TNF-α-induced pyroptosis during osteoblastic differentiation. Using in vitro cell cultures of preosteoblastic MC3T3-E1 cells, we found that TNF-α exposure causes cell pyroptosis in an inflammatory microenvironment during osteoblastic differentiation. Bioinformatics, protein docking model and co-immunoprecipitation analysis revealed an association between ELP2, STAT3 and NLRP3. Forced ELP2 expression promoted MC3T3-E1 cells pyroptosis, with an increase in the expression of STAT3, NLRP3 inflammasome, GSDMD/GSDME, osteoblast marker genes, and the activity of alkaline phosphatase. In contrast, ELP2 silencing ameliorated MC3T3-E1 cells pyroptosis, and osteogenic differentiation, especially after TNF-α stimulation. The TNF-α-induced cells pyroptosis during osteoblastic differentiation was therefore mediated by ELP2. These results suggest that ELP2 is upregulated at the pyroptosis of MC3T3-E1 cells and inhibits osteogenic differentiation in response to TNF-α through NLRP3-GSDMD/GSDME activation.
Topics: Cell Differentiation; NLR Family, Pyrin Domain-Containing 3 Protein; Osteoblasts; Osteogenesis; Pyroptosis; Tumor Necrosis Factor-alpha; Animals; Mice
PubMed: 37830762
DOI: 10.1111/jcmm.17994 -
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 -
Frontiers in Immunology 2023The tumor necrosis factor superfamily (TNFSF) and their receptors (TNFRSF) are important regulators of the immune system, mediating proliferation, survival,... (Review)
Review
The tumor necrosis factor superfamily (TNFSF) and their receptors (TNFRSF) are important regulators of the immune system, mediating proliferation, survival, differentiation, and function of immune cells. As a result, their targeting for immunotherapy is attractive, although to date, under-exploited. In this review we discuss the importance of co-stimulatory members of the TNFRSF in optimal immune response generation, the rationale behind targeting these receptors for immunotherapy, the success of targeting them in pre-clinical studies and the challenges in translating this success into the clinic. The efficacy and limitations of the currently available agents are discussed alongside the development of next generation immunostimulatory agents designed to overcome current issues, and capitalize on this receptor class to deliver potent, durable and safe drugs for patients.
Topics: Humans; Neoplasms; Receptors, Tumor Necrosis Factor; Tumor Necrosis Factor-alpha; Immune System; Immunotherapy
PubMed: 37180119
DOI: 10.3389/fimmu.2023.1147467 -
Methods in Molecular Biology (Clifton,... 2023The NACHT, LRR, and PYD domain-containing protein-3 (NLRP3) inflammasome activation is part of a stereotyped cellular response to injury or infection. The NLRP3...
The NACHT, LRR, and PYD domain-containing protein-3 (NLRP3) inflammasome activation is part of a stereotyped cellular response to injury or infection. The NLRP3 inflammasome activation promotes cellular dysfunction and death, leading to local and systemic inflammation, organ dysfunction, and adverse outcome. Immunohistochemistry and immunofluorescence can be used to determine whether the NLRP3 inflammasome components are present in human biopsy or autopsy tissue samples.
Topics: Humans; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Inflammation; Interleukin-1beta
PubMed: 37074644
DOI: 10.1007/978-1-0716-3040-2_8 -
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 -
International Journal of Environmental... Jan 2021NLRP3 inflammasome is one of the multimeric protein complexes of the nucleotide-binding domain, leucine-rich repeat (NLR)-containing pyrin and HIN domain family (PYHIN).... (Review)
Review
NLRP3 inflammasome is one of the multimeric protein complexes of the nucleotide-binding domain, leucine-rich repeat (NLR)-containing pyrin and HIN domain family (PYHIN). When activated, NLRP3 inflammasome triggers the release of pro-inflammatory interleukins (IL)-1β and IL-18, an essential step in innate immune response; however, defective checkpoints in inflammasome activation may lead to autoimmune, autoinflammatory, and metabolic disorders. Among the consequences of NLRP3 inflammasome activation is systemic chronic low-grade inflammation, a cardinal feature of obesity and insulin resistance. Understanding the mechanisms involved in the regulation of NLRP3 inflammasome in adipose tissue may help in the development of specific inhibitors for the treatment and prevention of obesity-mediated metabolic diseases. In this narrative review, the current understanding of NLRP3 inflammasome activation and regulation is highlighted, including its putative roles in adipose tissue dysfunction and insulin resistance. Specific inhibitors of NLRP3 inflammasome activation which can potentially be used to treat metabolic disorders are also discussed.
Topics: Humans; Inflammasomes; Interleukin-1beta; Metabolic Diseases; NLR Family, Pyrin Domain-Containing 3 Protein; Obesity
PubMed: 33435142
DOI: 10.3390/ijerph18020511 -
Gastroenterology Jul 2022
Topics: Humans; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor-alpha
PubMed: 35525321
DOI: 10.1053/j.gastro.2022.04.050 -
Cancer Discovery Sep 2022Interleukin-8 (CXCL8) produced in the tumor microenvironment correlates with poor response to checkpoint inhibitors and is known to chemoattract and activate...
UNLABELLED
Interleukin-8 (CXCL8) produced in the tumor microenvironment correlates with poor response to checkpoint inhibitors and is known to chemoattract and activate immunosuppressive myeloid leukocytes. In human cancer, IL8 mRNA levels correlate with IL1B and TNF transcripts. Both cytokines induced IL-8 functional expression from a broad variety of human cancer cell lines, primary colon carcinoma organoids, and fresh human tumor explants. Although IL8 is absent from the mouse genome, a similar murine axis in which TNFα and IL-1β upregulate CXCL1 and CXCL2 in tumor cells was revealed. Furthermore, intratumoral injection of TNFα and IL-1β induced IL-8 release from human malignant cells xenografted in immunodeficient mice. In all these cases, the clinically used TNFα blockers infliximab and etanercept or the IL-1β inhibitor anakinra was able to interfere with this pathogenic cytokine loop. Finally, in paired plasma samples of patients with cancer undergoing TNFα blockade with infliximab in a clinical trial, reductions of circulating IL-8 were substantiated.
SIGNIFICANCE
IL-8 attracts immunosuppressive protumor myeloid cells to the tumor microenvironment, and IL-8 levels correlate with poor response to checkpoint inhibitors. TNFα and IL-1β are identified as major inducers of IL-8 expression on malignant cells across cancer types and models in a manner that is druggable with clinically available neutralizing agents. This article is highlighted in the In This Issue feature, p. 2007.
Topics: Animals; Cytokines; Humans; Infliximab; Interleukin-1beta; Interleukin-8; Mice; Tumor Microenvironment; Tumor Necrosis Factor-alpha
PubMed: 35771565
DOI: 10.1158/2159-8290.CD-21-1115