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International Journal of Molecular... Nov 2022Cancer is a major cause of death worldwide and especially in high- and upper-middle-income countries. Despite recent progress in cancer therapies, such as chimeric... (Review)
Review
Cancer is a major cause of death worldwide and especially in high- and upper-middle-income countries. Despite recent progress in cancer therapies, such as chimeric antigen receptor T (CAR-T) cells or antibody-drug conjugate (ADC), new targets expressed by the tumor cells need to be identified in order to selectively drive these innovative therapies to tumors. In this context, IL-1RAP recently showed great potential to become one of these new targets for cancer therapy. IL-1RAP is highly involved in the inflammation process through the interleukins 1, 33, and 36 (IL-1, IL-33, IL-36) signaling pathways. Inflammation is now recognized as a hallmark of carcinogenesis, suggesting that IL-1RAP could play a role in cancer development and progression. Furthermore, IL-1RAP was found overexpressed on tumor cells from several hematological and solid cancers, thus confirming its potential involvement in carcinogenesis. This review will first describe the structure and genetics of IL-1RAP as well as its role in tumor development. Finally, a focus will be made on the therapies based on IL-1RAP targeting, which are now under preclinical or clinical development.
Topics: Humans; Neoplasms; Interleukin-1
PubMed: 36499246
DOI: 10.3390/ijms232314918 -
Zeitschrift Fur Rheumatologie Feb 2019Schnitzler syndrome is a very rare acquired systemic disease with many similarities to hereditary autoinflammatory syndromes. The main characteristics are generalized...
Schnitzler syndrome is a very rare acquired systemic disease with many similarities to hereditary autoinflammatory syndromes. The main characteristics are generalized exanthema and a monoclonal gammopathy with IgM. Other clinical features include fever, muscle, bone and/or joint pain, and lymphadenopathy. About 15-20% of patients with Schnitzler syndrome develop lymphoproliferative diseases and, in rare cases, amyloid A (AA) amyloidosis can occur if the disease is not treated. Activation of the innate immune system, especially interleukin(IL)-1β, is central in the pathogenesis of the disease. Consequently, complete control of disease symptoms can be achieved in 80% of patients by treatment with the IL-1 receptor antagonist anakinra.
Topics: Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin-1beta; Schnitzler Syndrome
PubMed: 30666414
DOI: 10.1007/s00393-019-0591-1 -
The Journal of Experimental Medicine Mar 2018In this issue of JEM, Boucher et al. (https://doi.org/10.1084/jem.20172222) report isolation of active caspase-1 from macrophages after inflammasome activation....
In this issue of JEM, Boucher et al. (https://doi.org/10.1084/jem.20172222) report isolation of active caspase-1 from macrophages after inflammasome activation. Surprisingly, they find that caspase-1 is quickly inactivated upon autoproteolytic processing.
Topics: Caspase 1; Inflammasomes; Interleukin-1beta; Macrophages
PubMed: 29440361
DOI: 10.1084/jem.20180241 -
Anatolian Journal of Cardiology Mar 2018
Topics: Humans; Interleukin-1; Multigene Family; No-Reflow Phenomenon; Polymorphism, Genetic
PubMed: 29521323
DOI: No ID Found -
MMW Fortschritte Der Medizin Nov 2021
Topics: Humans; Rheumatic Diseases; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor-alpha
PubMed: 34767199
DOI: 10.1007/s15006-021-0519-y -
Cytokine Sep 2022Cellular communication mediated by cytokines is an important mechanism dictating immune responses, their cross talk and final immune output. Cytokines play a major role... (Review)
Review
Cellular communication mediated by cytokines is an important mechanism dictating immune responses, their cross talk and final immune output. Cytokines play a major role in dictating the immune outcome to cancer by regulating the events of development, differentiation and activation of innate immune cells. Cytokines are pleiotropic in nature, hence understanding their role individually or as member of network cytokines is critical to delineate their role in tumour immunity. Tumour systemically manipulates the immune system to evade and escape immune recognition for their uncontrollable growth and metastasis. The developing tumour comprise a large and diverse set of myeloid cells which are vulnerable to manipulation by the tumour-microenvironment. The innate immune cells of the monocytic lineage skew the fate of the adaptive immune cells and thus dictating cancer elimination or progression. Targeting cells at tumour cite is preposterous owing to their tight network, poor reach and abundance of immunosuppressive mechanisms. Monocytic lineage-derived cytokines (monokines) play crucial role in tumour regression or progression by either directly killing the tumour cells with TNFα or promoting its growth by TGFβ. In addition, the monokines like IL-12, IL-1β, IL-6, IL-10 and TGFβ direct the adaptive immune cells to secrete anti-tumour cytokines, TNFα, IFNγ, perforin and granzyme or pro-tumour cytokines, IL-10 and TGFβ. In this review, we elucidate the roles of monokines in dictating the fate of tumour by regulating responses at various stages of generation, differentiation and activation of immune cells along with the extensive cross talk. We have attempted to delineate the synergy and antagonism of major monokines among themselves or with tumour-derived or adaptive immune cytokines. The review provides an update on the possibilities of placing monokines to potential practical use as cytokine therapy against cancer.
Topics: Cytokines; Humans; Interleukin-10; Monocytes; Monokines; Neoplasms; Transforming Growth Factor beta; Tumor Microenvironment; Tumor Necrosis Factor-alpha
PubMed: 35764025
DOI: 10.1016/j.cyto.2022.155948 -
IUBMB Life May 2015Acute brain injuries such as caused by stroke are amongst the leading causes of death and are the leading cause of disability. Despite this there are very limited... (Review)
Review
Acute brain injuries such as caused by stroke are amongst the leading causes of death and are the leading cause of disability. Despite this there are very limited therapeutic options, and new therapeutic strategies and targets are required. Inflammation is known to exacerbate brain injury and is now considered as a potential therapeutic target. The damaging inflammation that occurs after acute brain injury is driven by pro-inflammatory members of the interleukin (IL)-1 cytokine family, namely, IL-1α and IL-1β. Previous research efforts have focussed on the biology and contribution of IL-1β. However, we now recognise that IL-1α is an early and important mediator of inflammation after injury. This review focuses on what is known about IL-1α, its regulation and its contribution to brain injury. Inhibiting mechanisms regulating the processing and release of IL-1α may offer new therapeutic targets for the treatment of devastating acute brain injuries.
Topics: Cell Death; Encephalitis; Humans; Interleukin-1alpha
PubMed: 25906979
DOI: 10.1002/iub.1377 -
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 -
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 -
Arteriosclerosis, Thrombosis, and... Nov 2018
Topics: Humans; Thrombosis; Tumor Necrosis Factor-alpha
PubMed: 30354242
DOI: 10.1161/ATVBAHA.118.311660