MAP Kinase Signaling at the Crossroads of Inflammasome Activation

Immunological Reviews, Journal Year: 2025, Volume and Issue: 329(1)

Published: Jan. 1, 2025

ABSTRACT Inflammasomes are crucial mediators of both antimicrobial host defense and inflammatory pathology, requiring stringent regulation at multiple levels. This review explores the pivotal role mitogen‐activated protein kinase (MAPK) signaling in modulating inflammasome activation through various regulatory mechanisms. We detail recent advances understanding MAPK‐mediated NLRP3 priming, licensing activation, with emphasis on MAPK‐induced activator protein‐1 (AP‐1) ERK1 JNK licensing, TAK1 connecting death receptor to activation. Furthermore, we discuss novel insights into MAPK human NLRP1 focusing MAP3K member ZAKα as a key linking ribosomal stress Lastly, work elucidating how Bacillus anthracis lethal toxin (LeTx) manipulates induce macrophage apoptosis an immune evasion strategy, counteraction this effect genotype‐specific Nlrp1b certain rodent strains.

Language: Английский

---

Unveiling the impact of CD133 on cell cycle regulation in radio- and chemo-resistance of cancer stem cells

Frontiers in Public Health, Journal Year: 2025, Volume and Issue: 13

Published: Feb. 6, 2025

The adaptation of malignancy to therapy presents a significant challenge in cancer treatment. cell cycle plays crucial role regulating the evolution radio- and chemo-resistance tumor cells. Cancer stem cells (CSCs) are primary source resistance, with CD133 being one most recognized valuable surface markers CSCs. Evidence increasingly suggests that is associated resistance. current understanding molecular biological function limited, leading ongoing debates about its biology. In this review, we explore recent research emerging trends related through extensive literature content analysis. It was summarized new insights into relationships signaling pathways resistant aim review provide foundational how these their interactions impact prognosis inform treatment strategies.

Language: Английский

---

C-reactive protein-induced injury in Mycoplasma pneumoniae -infected lung epithelial cells is mediated by the P38 MAPK/mitochondrial apoptosis pathway

Microbiology Spectrum, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 11, 2025

Patients with Mycoplasma pneumoniae (MP) infections have markedly higher C-reactive protein (CRP). We investigated how CRP contributes to lung epithelial cell death following MP infection. levels were assessed in children diagnosed pneumonia (MPP) and A549 cells infected MP. genetically modified overexpress CRP. Effects on viability, apoptosis, reactive oxygen species (ROS) mitochondrial membrane potential (ΔΨm) evaluated. The expression of proteins implicated the p38 MAPK/mitochondrial apoptotic pathway was analyzed. protective effects MAPK inhibitor SB203580 protector cyclosporin A (CsA) assessed. elevated both MPP patients MP-infected compared controls. Increased apoptosis reduced viability observed cells. overexpression led upregulation pathway, increased cytoplasmic Cyt C, decreased Tom 20 ΔΨm, ROS. Pretreatment or posttreatment CsA damage enhanced survival. during infection promote by activating pathway. Targeting this could offer therapeutic reduce patients.IMPORTANCEThis study provides critical information understanding pathophysiological mechanisms for concerning mediating injury. This outlines significant increase shows its direct involvement through By explaining possibility targeting connected signaling devise interventions amelioration is brought light. implications such data are not merely added knowledge disease pathobiology but also it brings new promise novel intervention strategies result improved clinical outcomes. elucidation specific molecular targets inside heralds a area regarding direction future research application humanity general broader relevance impact respiratory diseases.

Language: Английский

---

Prospects of compounds of herbal plants as anticancer agents: a comprehensive review from molecular pathways

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

Published: July 22, 2024

Cancer refers to the proliferation and multiplication of aberrant cells inside human body, characterized by their capacity proliferate infiltrate various anatomical regions. Numerous biochemical pathways signaling molecules have an impact on cancer auto biogenesis process. The regulation crucial cellular processes necessary for cell survival proliferation, which are triggered phytochemicals, is significantly influenced pathways. These or components regulated phytochemicals. Medicinal plants a significant reservoir diverse anticancer medications employed in chemotherapy. effects phytochemicals mediated several methods, including induction apoptosis, cessation cycle, inhibition kinases, prevention carcinogenic substances. This paper analyzes phytochemistry seven prominent plant constituents, namely, alkaloids, tannins, flavonoids, phenols, steroids, terpenoids, saponins, focusing involvement MAPK/ERK pathway, TNF signaling, death receptors, p53, p38, actin dynamics. Hence, this review has examined range encompassing structural characteristics potential mechanisms. It underscored significance plant-derived bioactive compounds cancer, utilizing molecular In addition, endeavor also seeks incentivize scientists carry out clinical trials derived from plants.

Language: Английский

---

Mitogen-Activated Protein Kinase: A Potent Signaling Protein that Combats Biotic and Abiotic Stress in Plants

Journal of Plant Growth Regulation, Journal Year: 2024, Volume and Issue: 43(6), P. 1762 - 1786

Published: Feb. 22, 2024

Language: Английский

---

Cellular Senescence and Inflammaging in the Bone: Pathways, Genetics, Anti-Aging Strategies and Interventions

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7411 - 7411

Published: July 5, 2024

Advancing age is associated with several age-related diseases (ARDs), musculoskeletal conditions impacting millions of elderly people worldwide. With orthopedic contributing towards considerable number patients, a deeper understanding bone aging the need hour. One underlying factors cellular senescence and its secretory phenotype (SASP). SASP comprises pro-inflammatory markers, cytokines chemokines that arrest cell growth development. The accumulation over years leads to chronic low-grade inflammation advancing age, also known as inflammaging. pathways molecular mechanisms focused on inflammaging are currently limited but increasingly being explored. Most genes, involved in coincide those cancer other ARDs like osteoarthritis (OA). Thus, exploring these using techniques sequencing, identifying combatting them most suitable approach crucial for healthy early detection ARDs. Several approaches can be used aid regeneration reduce bone. These may pharmacological, non-pharmacological lifestyle interventions. increasing evidence intricate relationship between aging, senescence, ARDs, anti-aging strategies marrow (BM).

Language: Английский

---

Mechanism of Reactive Oxygen Species-Guided Immune Responses in Gouty Arthritis and Potential Therapeutic Targets

Biomolecules, Journal Year: 2024, Volume and Issue: 14(8), P. 978 - 978

Published: Aug. 9, 2024

Gouty arthritis (GA) is an inflammatory disease caused by monosodium urate (MSU) crystals deposited in the joint tissues causing severe pain. The can recur frequently and tends to form tophus joints. Current therapeutic drugs for acute phase of GA have many side effects limitations, are unable prevent recurrent attacks formation, overall efficacy unsatisfactory. Therefore, we need advance research on microscopic mechanism seek safer more effective through relevant targets block process. shows that pathogenesis closely related NLRP3 inflammation, oxidative stress, MAPK, NET, autophagy, Ferroptosis. However, after synthesizing sorting out above mechanisms, it found presence ROS throughout almost entire spectrum micro-mechanisms gout process, which combines multiple immune responses a large network diagram complex tight connections involved studies shown cell necrosis, pathological signs be effectively suppressed modulating network-related targets. In this article, one hand, investigated generative generation its association with GA. On other explored potential treatment prevention provide reference ideas development highly

Language: Английский

---

Ursonic Acid Ameliorates H2O2-Induced Oxidative Damage in PC12 Cells and Prolonged the Lifespan in C. elegans by Activating MAPKs/Nrf2/HO-1 Signaling Pathway

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 23, 2025

Language: Английский

---

Enhancing the effectiveness of immunotherapy in rheumatoid arthritis by delaying immunosenescence triggered by fibroblast-like synoviocytes

Journal of Orthopaedic Surgery and Research, Journal Year: 2025, Volume and Issue: 20(1)

Published: Jan. 23, 2025

Rheumatoid arthritis (RA) is a prevalent autoimmune disorder primarily targeting the diarthrodial joints. During progression of RA, fibroblast-like synoviocytes (FLSs) exhibit tumor-like behavior, including increased proliferation, inflammation mediation, and aggressive phenotypes, leading to bone erosion. Additionally, T cells in RA acquire pro-inflammatory characteristics, exacerbating inflammatory environment affected joints associated tissues. Notably, senescent contribute inflammation, further accelerating disease process. Metabolic changes rheumatoid FLSs not only maintain their properties but also trigger cascades, particularly affecting lymphocytes. This review examines molecular alterations context systemic immune aging, with focus on thymic insufficiency-associated cell senescence, explores potential therapeutic avenues.

Language: Английский

---

MK2 Inhibition in CD4+ T Cells Protects Against IFNγ and IL-17A, Chronic Inflammation, and Fibrosis in Inflammatory Bowel Disease Models

Inflammatory Bowel Diseases, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 12, 2025

Abstract Background CD4+ T cells contribute to chronic inflammation and fibrosis in inflammatory bowel disease (IBD), but the cellular mechanisms remain elusive. We have found that mitogen-activated protein kinase 2 (MK2) pathway plays a major role overall pathology IBD. Thus, here, we examined of MK2 regulating cell responses IBD models. Methods Interleukin-10 (IL-10) knockout (KO) mice treated with inhibitors (MK2i) CD4-specific knockdown dextran sodium sulfate (DSS) treatments were used examine by multiplex array, gene expression, flow cytometry, histology. Human tissues MK2i Th1 Th17 markers. Results IL-10 KO therapeutically showed significantly reduced interferon gamma (IFNγ) interleukin-17A (IL-17A) number IFNγ+ IL-17A+ producing cytometry. To investigate direct during IBD, utilized DSS colitis. A decrease colonic inflammation, IFNγ IL-17, pro-fibrotic genes, extracellular matrix deposition was observed compared control mice. Additionally, IL-17A directly regulated expression genes colon tissues. Conclusions The regulates models is potential therapeutic target.

Language: Английский

---