Interleukin-38 and Insulin Resistance

Endocrine Metabolic & Immune Disorders - Drug Targets, Journal Year: 2023, Volume and Issue: 24(6), P. 611 - 616

Published: Sept. 13, 2023

Insulin resistance, i.e., decreased biological response to insulin, is a risk factor for many diseases, such as obesity, type 2 diabetes (T2DM), cardiovascular disease, polycystic ovary syndrome, some forms of cancer and neurodegenerative diseases. One its main causes chronic low-grade inflammation, mediated by the proinflammatory pathways, c-Jun N-terminal kinase (JNK) pathway nuclear kappa B (NFκB) pathway. Interleukin (IL)-38 (IL-38) newly discovered cytokine that belongs IL-1 family. There are three hypothetical pathways through which IL-38 may bind specific receptors inhibit their activity. Those associated with IL-36 receptor (IL-36R), accessory protein-like 1 (IL1RAPL1) (IL1R1). studies linking improve insulin sensitivity difference in serum patients resistance or correlation concentrations indexes. However, questions still remain regarding activity itself role pathogenesis resistance. The goal this study showcase IL-38, activity, hypothesized signaling connection future perspectives research on IL-38. We present can be potential target treatment

Language: Английский

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Identifying biomarkers deciphering sepsis from trauma-induced sterile inflammation and trauma-induced sepsis

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 12, 2024

Objective The purpose of this study was to identify a panel biomarkers for distinguishing early stage sepsis patients from non-infected trauma patients. Background Accurate differentiation between trauma-induced sterile inflammation and real infective poses complex life-threatening medical challenge because their common symptoms albeit diverging clinical implications, namely different therapies. timely accurate identification in is therefore vital ensure prompt tailored interventions (provision adequate antimicrobial agents if possible eradication foci) that can ultimately lead improved therapeutic management patient outcome. withholding antimicrobials without also important aspects both environmental perspective. Methods In proof-of-concept study, we employed advanced technologies, including Matrix-Assisted Laser Desorption/Ionization (MALDI) multiplex antibody arrays (MAA) actual inflammation. Results By comparing groups (controls, infected septic shock under mechanical ventilation) at time points, uncovered distinct protein patterns associated with on the one hand other hand. SYT13 IL1F10 emerged as potential biomarkers, while reduced levels A2M were indicative conditions. Additionally, higher TREM1 later Furthermore, enrichment analyses revealed differences inflammatory response sepsis, proteins related complement coagulation cascades being elevated whereas relevant focal adhesion diminished sepsis. Conclusions Our findings, therefore, suggest combination needed development novel diagnostic approaches deciphering

Language: Английский

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The Role of Genetics and Epigenetic Regulation in the Pathogenesis of Osteoarthritis

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(14), P. 11655 - 11655

Published: July 19, 2023

Osteoarthritis (OA) is progressive disease characterised by cartilage degradation, subchondral bone remodelling and inflammation of the synovium. The associated with obesity, mechanical load age. However, multiple pro-inflammatory immune mediators regulate expression metalloproteinases, which take part in degradation. Furthermore, genetic factors also contribute to OA susceptibility. Recent studies have highlighted that epigenetic mechanisms may OA-associated genes. This review aims present pathogenesis summarise current evidence regarding role genetics epigenetics this process.

Language: Английский

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Exploring the clinical significance of IL-38 correlation with PD-1, CTLA-4, and FOXP3 in colorectal cancer draining lymph nodes

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: March 12, 2024

Introduction Colorectal cancer (CRC) presents a substantial challenge characterized by unacceptably high mortality and morbidity, primarily attributed to delayed diagnosis reliance on palliative care. The immune response of the host plays pivotal role in carcinogenesis, with IL-38 emerging as potential protective factor CRC. However, precise involvement among various leucocytes, its interactions PD-1/PD-L1, impact metastasis require further elucidation. Results Our investigation revealed significant correlation between expression metastasis, particularly concerning survival diverse leucocytes within draining lymph nodes. In mesentery nodes, we observed an inverse stages node invasions (TNM), invasion depth, distance, differentiation. This aligns overall advantage associated higher CRC patients’ nodes compared lower levels, well elevated CD4 + or CD8 cells. Notably, distinct subset patients /PD-1 low exhibited superior outcomes other combinations. Discussion findings demonstrate that colorectal regional from is inversely correlated PD-1/PD-L1 but positively infiltrating lymphocytes. combined assessment PD-1 emerges promising biomarker for predicting prognosis

Language: Английский

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IL-38 promotes the development of prostate cancer

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: May 8, 2024

Introduction Prostate Cancer (PCa) remains a significant concern in male cancer-related mortality. Tumour development is intricately regulated by the complex interactions between tumour cells and their microenvironment, making it essential to determine which is/are key factor(s) that influence progression of PCa within microenvironment. Materials methods The current study utilised histopathology immunohistochemistry expression IL-38 analysed correlation level clinical pathological characteristics. Results There was increase tissues compared adjacent non-PCa (P < 0.0001). In addition, significantly higher with high proliferation index those low value-added index. ROC curve analysis demonstrated has specificity sensitivity for diagnosis (AUC=0.76). Moreover, we Probed cellular source prostate cancer tissue immunofluorescence double staining. Additionally, PCa, inversely correlated levels CD8 PD-1. Survival revealed lower overall survival rate patients (P=0.0069), when co-expressed CD8, /CD8 group decreased significantly. Multivariate indicated TNM staging were independent predictors patients. Conclusion These findings suggest plays crucial role exploration various immune factors microenvironment further reveals its mechanism action, potential target immunotherapy PCa.

Language: Английский

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IL-1RAP, a Key Therapeutic Target in Cancer

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(23), P. 14918 - 14918

Published: Nov. 29, 2022

Cancer is a major cause of death worldwide and especially in high- upper-middle-income countries. Despite recent progress cancer therapies, such as chimeric antigen receptor T (CAR-T) cells or antibody-drug conjugate (ADC), new targets expressed by the tumor need to be identified order selectively drive these innovative therapies tumors. In this context, IL-1RAP recently showed great potential become one for therapy. highly involved inflammation process through interleukins 1, 33, 36 (IL-1, IL-33, IL-36) signaling pathways. Inflammation now recognized hallmark carcinogenesis, suggesting that could play role development progression. Furthermore, was found overexpressed on from several hematological solid cancers, thus confirming its involvement carcinogenesis. This review will first describe structure genetics well development. Finally, focus made based targeting, which are under preclinical clinical

Language: Английский

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Full-length and N-terminally truncated recombinant interleukin-38 variants are similarly inefficient in antagonizing interleukin-36 and interleukin-1 receptors

Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 20, 2025

Interleukin (IL)-38 is an IL-1 family cytokine that was proposed to exert anti-inflammatory effects. However, its mechanisms of action are not well understood and the identity IL-38 receptor(s) remains debated. Proposed candidates include receptor (IL-1R1), IL-36 (IL-36R) orphan IL-1RAPL1. Yet, in literature, often presented as IL-36R antagonist. The N-terminus protein produced a human keratinocyte cell line endogenous epidermal isolated from healthy skin characterized by mass spectrometry. effects various recombinant forms on IL-36R- IL-1R1-mediated responses were assessed HEK Blue reporter cells normal line. IL-8 IL-6 production quantified ELISA. Binding proteins surface plasmon resonance. Analysis native revealed keratinocytes starts at cysteine 2. In cell-based assays, neither full-length amino acid 2-152 nor two N-terminally truncated showed efficient antagonist activity responses. bound with only moderate affinity, which may provide mechanistic explanation for inefficient antagonism. Our results argue against meaningful inhibitory any variants tested or underlying reported thus still unclear, but seem unlikely be mediated classical IL-1R1

Language: Английский

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Interleukin-38 as a potential diagnostic biomarker for heart failure

Biomarkers in Medicine, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 7

Published: Feb. 13, 2025

Interleukin-38 (IL-38) attenuates inflammation, myocardial injury, and ventricular remodeling after infarction, which potentially reduces the incidence of heart failure (HF). This study aimed to evaluate diagnostic value IL-38 for HF. was detected via enzyme-linked immunosorbent assay in serum samples 238 hF patients 30 healthy controls when enrollment. elevated HF compared with (p = 0.002). Receiver operating characteristic (ROC) analysis showed that area under curve (AUC) predicting risk 0.676 (95% confidence interval 0.594-0.758). The Youden index diagnosing peaked at 0.329 cutoff set as 6 ng/mL, sensitivity specificity 0.833 0.496, respectively. Before (odds ratio 1.493, p 0.002) 1.500, 0.007) adjustment age gender by multivariable regression analysis, associated a higher risk. Moreover, combination possessed good (AUC 0.796, 95% 0.706-0.885). is increased controls, its shows diagnosis

Language: Английский

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The distinct roles of IL-37 and IL-38 in non-small cell lung carcinoma and their clinical implications

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 21, 2025

Lung cancer, a significant global health challenge, is primarily classified into non-small cell lung cancer (NSCLC) and small cancer. Despite advancements in targeted therapies immunotherapies, NSCLC outcomes remain poor, with low five-year survival rates. Given the lung’s constant exposure to environment presence of mucosal-associated lymphoid tissues, immunity plays crucial role development. Immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 have shown promise. However, adverse immune events limit their efficacy. This review highlights contrasting roles IL-37 IL-38 pathogenesis. IL-37, an anti-inflammatory cytokine, suppresses tumour growth. It achieves this by modulating macrophage polarization dendritic maturation. Correlations between intra-tumoral expression improved suggest protective NSCLC. may be mediated through VEGF inhibition regulation. Conversely, IL-38, while certain contexts, exhibits pro-tumorigenic enhances progression increasing pro-inflammatory cytokine secretion facilitating evasion, potentially NF-κB signalling. Notably, negatively regulates further promoting tumorigenesis. Emerging data that has therapeutic potential inhibiting metastasis supporting modulation. In contrast, presents target for mitigating microenvironment effects. The distinct these cytokines emphasize complex dynamics Further exploration molecular mechanisms implications warranted. Targeting offer novel strategies enhancing treatment

Language: Английский

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IL-38 blockade induces anti-tumor immunity by abrogating tumor-mediated suppression of early immune activation

mAbs, Journal Year: 2023, Volume and Issue: 15(1)

Published: May 22, 2023

Immune checkpoint inhibitors that overcome T cell suppressive mechanisms in tumors have revolutionized the treatment of cancer but are only efficacious a small subset patients. Targeting acting on innate immune cells could significantly improve incidence clinical response by facilitating multi-lineage against tumor involving both adaptive and systems. Here, we show intra-tumoral interleukin (IL)-38 expression is feature large frequency head neck, lung cervical squamous cancers correlates with reduced numbers. We generated IMM20324, an antibody binds human mouse IL-38 proteins inhibits binding to its putative receptors, 1 receptor accessory protein-like (IL1RAPL) IL-36R. In vivo, IMM20324 demonstrated good safety profile, delayed growth mice EMT6 syngeneic model breast cancer, inhibited expansion B16.F10 melanoma model. Notably, resulted prevention following re-implantation cells, indicating induction immunological memory. Furthermore, exposure correlated decreased volume increased levels chemokines. Together, our data suggest expressed high patients allows suppress anti-tumor immunity. Blockade activity using can re-activate immunostimulatory microenvironment leading infiltration, generation tumor-specific memory abrogation growth.

Language: Английский

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