Inflammation Research最新文献

Introduction: The clinical relevance of circulating inflammatory proteins in Immunoglobulin A nephropathy (IgAN) remains incompletely defined. We examined whether serum inflammatory proteins-particularly tumor necrosis factor (TNF) receptor-related markers-track with disease severity and progression in IgAN.

Methods: We enrolled Japanese subjects undergoing native kidney biopsy with newly diagnosed IgAN (n = 134); disease controls with membranous nephropathy (n = 24), minimal change disease (n = 45), or lupus nephritis (n = 23); and healthy controls (n = 88). We measured 10 serum inflammatory proteins before renal biopsy and evaluated their levels in different glomerulonephritis. Additionally, we assessed associations between these proteins and clinical outcomes, including kidney function and histological changes in IgAN.

Results: Inflammatory proteins, especially TNF-R1, TNF-R2, TNF-R3, TNF-R7, and TNF-R27, were elevated in patients with IgAN and were associated with the severity of tubulointerstitial lesions. Among disease controls, membranous nephropathy and lupus nephritis also showed elevated TNF-receptor-related proteins, whereas minimal change disease did not. TNF-R7 showed a significant early increase, suggesting possible involvement in IgAN pathogenesis. Multivariable analysis indicated these proteins could predict kidney function decline.

Conclusions: Specific circulating inflammatory proteins, particularly in the TNF receptor pathway, reflect disease activity and structural injury in IgAN and may help identify patients at higher risk of progression.

Systemic sclerosis is an autoimmune connective tissue disease of unknown cause and diverse clinical manifestations. Vasospastic episodes (Raynaud's phenomenon), often triggered by cold or stress, typically appear at disease onset. Cytokines, particularly TGF-β, act in the inflammatory and hypoxic microenvironment to drive fibrosis, which predominantly develops at inflammatory sites. Several cell types contribute to disease pathogenesis and fibrosis, including vascular endothelial cells, vascular smooth muscle cells, and fibroblasts in the extracellular matrix. Multiple signaling pathways are activated in these cells and promote disease progression. Endothelial and vascular smooth muscle cells respond to diverse ligands through pathways such as AKT, MAPK, and GPCR signaling, which promote fibrosis progression in the profibrotic and proinflammatory milieu. Cytokines are also important mediators of inflammation and fibrosis, particularly by acting on activated monocytes in the ECM and guiding them toward M1 or M2 macrophage polarization. In the early inflammatory stage, M1 macrophages predominate, while the fibrotic stage is characterized by increased M2 macrophage presence. ECM accumulation, resulting from TGF-β signaling in fibroblasts, provides integrins with ligands and promotes enhanced adhesion and migration of these cells. TGF-β, on the other hand, can transactivate the Ras pathway, promoting myofibroblast differentiation and enhancing pro-fibrotic effects.

Objective and design: Astilbin (ATB) is a newly discovered natural compound with anti-inflammatory and immunomodulatory effects. However, its effects and underlying mechanisms in acute lung injury (ALI) remain unclear.

Material or subjects: An ALI model was established by intratracheal injection of lipopolysaccharide (LPS) into the trachea of C57BL/6 mice. In vitro, MLE-12 cells were stimulated with LPS. ATB was administered as a pretreatment to C57BL/6 mice and MLE-12 cells.

Results: ATB significantly alleviated ALI and suppressed the inflammatory response induced by LPS. Further data suggested that ATB inhibited LPS-induced ferroptosis in epithelial cells by increasing GPX4 and xCT expression. Moreover, ATB promoted NRF2 nuclear translocation in the LPS-treated group, while NRF2 inhibition significantly reversed the protective effects of ATB on ferroptosis and inflammation. NRF2 knockout in vivo abolished the protective effects of ATB against ALI and epithelial cell ferroptosis. Mechanistically, ATB increased NRF2 activity by binding to the Val608 amino acid of NRF2. The effect of ATB in improving ALI and ferroptosis was significantly reduced in NRF2 Val608 mutant mice.

Conclusion: ATB mitigated ALI by suppressing epithelial cell ferroptosis and activating the NRF2 pathway via binding to Val608 of NRF2.

Background: Clopidogrel resistance remains a significant clinical challenge in coronary artery disease (CAD), with traditional explanations focusing on CYP450 polymorphisms. However, emerging evidence highlights the critical role of inflammation and angiogenesis in modulating platelet reactivity and clopidogrel responsiveness. Genetic variants in these pathways may represent under recognized determinants of treatment failure. This pilot study investigated the association between single nucleotide polymorphisms (SNPs) in inflammation- (CCR2, CCL5, CCL2) and angiogenesis-related (KDR, VEGFA) genes and clopidogrel resistance.

Methods: In a cross-sectional study of 135 Tunisian CAD patients on dual antiplatelet therapy, clopidogrel response was assessed using VerifyNow P2Y12 assay (resistance defined as PRU  ≥  208). Nine SNPs were genotyped via PCR-RFLP. Associations were evaluated using logistic regression, adjusting for covariates.

Results: The CCL5 rs2280789-C allele conferred a 3.4-fold increased resistance risk (OR = 3.40 (1.54-7.48), p =  0.002), while the CCR2 rs1799864-A allele was protective (OR =  0.30 (0.10-0.84), p =  0.02). The KDR rs1870377-AA genotype tripled resistance odds (OR =  3.05 (1.05-8.83), p =  0.04). A polygenic model revealed synergistic effects: 53% of non-responders carried  ≥ 2 risk genotypes (CCR2-GG, CCL5-TC, KDR-AA) vs. 15% of responders (OR = 6.51 (2.86-14.83), p < 0.001). No associations were found for VEGFA or CCL2 SNPs.

Conclusion: Beyond CYP450-mediated metabolism, clopidogrel resistance is driven by immuno-vascular mechanisms involving CCL5-mediated thrombo-inflammation, CCR2-dependent monocyte recruitment, and VEGFR2-linked endothelial dysfunction. These findings advocate for precision antiplatelet strategies integrating inflammatory and angiogenic pathways to optimize therapy.

Objective: The aim of this study was to investigate whether antigen-specific reduced IgG inhibits mast cell activation evoked by the aggregation of the high-affinity IgE receptor (FcεRI) in a manner similar to intact IgG.

Materials: Rat basophilic leukemia (RBL-2H3) cells are used for a mast cell model.

Treatment: Monovalent mouse anti-trinitrophenyl (TNP) IgG1 (75 kDa) was prepared by reducing the disulfide bond between the heavy chains using cysteamine hydrochloride. IgE-sensitized RBL-2H3 cells were stimulated with TNP-OVA, and reduced IgG1 was added 5 min after stimulation.

Methods: Degranulation and IL-4 secretion were measured 30 min and 3 h after TNP-OVA stimulation by β-hexosaminidase assay and ELISA, respectively. The intracellular distribution of SH2-containing inositol 5'-phosphatase 1 (SHIP1) was determined using immunostaining. Group differences were analyzed using the Tukey-Kramer test.

Results: Reduced IgG1 significantly inhibited degranulation and IL-4 secretion in antigen-stimulated RBL-2H3 cells to an extent similar to intact IgG1. Intracellular SHIP1 localized to the plasma membrane 5 min after the addition of reduced IgG1, mirroring the effect of intact IgG1.

Conclusions: These results suggest that antigen-specific reduced IgG1 (monovalent) inhibits antigen-induced mast cell activation by activating SHIP1 through co-ligation of FcεRI and the low-affinity IgG receptor (FcγRIIB).

Background: In a ligature-induced periodontitis rat model, we tested oral citral (100 mg/kg, gavage) for 6 or 14 days and quantified alveolar bone loss, gingival cytokines, nitric oxide (NO), reactive oxygen species (ROS), MMP-2 activity, and plasma TNF-α.

Methods: Adult male rats received a ligature around the first lower right molar for 7 or 15 days to induce periodontitis, while control animals remained unligated. Alveolar bone loss was assessed by measuring the cementoenamel junction-bone crest distance. Gingival cytokines (TNF-α, IL-1β, IL-6, IL-10) and plasma TNF-α were determined by ELISA, gingival NO by chemiluminescence, MMP-2 activity by gelatin zymography, and local ROS by in situ detection.

Results: Citral did not affect healthy gingiva. In ligature-induced periodontitis, a 14-day citral treatment significantly reduced alveolar bone loss, downregulated pro-inflammatory cytokines, increased IL-10, decreased plasma TNF-α levels, and inhibited both NO production and MMP-2 activity. ROS accumulation in the gingival tissue was also attenuated.

Conclusion: These findings suggest that oral citral exhibits anti-inflammatory and antioxidant effects, thereby limiting alveolar bone loss in experimental periodontitis.

The study by Bai and Guo (Biol Direct 20(1):73. https://doi.org/10.1186/s13062-025-00669-0 , 2025) offers significant insights into the molecular mechanisms of LPS tolerance in macrophages. The authors identify a novel pathway wherein the transcription factor SPI1 (PU.1) directly upregulates the expression of the inhibitory receptor LILRB2, which in turn suppresses TLR8-mediated MyD88/NF-κB signaling to reinforce an immunosuppressive phenotype. While this work elegantly connects transcriptional regulation with functional immune modulation, several aspects warrant further discussion. The broad role of SPI1 necessitates confirming the specificity of its action on LILRB2 and excluding indirect effects on other tolerance regulators. The unconventional inhibition of TLR8, an endosomal viral RNA sensor, by LILRB2 raises questions about ligand specificity and context, particularly in scenarios of viral co-infection. Furthermore, the dominant role of TLR8 in LPS tolerance, a process canonically initiated by TLR4, merits additional validation to clarify its universality. Translational targeting of the SPI1/LILRB2 axis holds promise for reversing immune paralysis in sepsis or chronic inflammation, but potential risks demand careful evaluation using cell-specific approaches. Future work integrating epigenetic analyses, structural studies, single-cell transcriptomics from patients, and investigation of crosstalk with other immunoregulatory pathways will be crucial to fully establish the biological and clinical significance of these findings.

Background: Aquaporins (AQPs) are a class of channel proteins expressed on the cell membrane, responsible for facilitating the transport of water molecules and certain small solutes across the membrane. Their dysregulation is involved in the occurrence and progression of major lung diseases.

Findings: We systematically reviewed the expression and functional alterations of AQPs in acute lung injury (ALI), pneumonia, asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis (PF) and lung cancer, and integrated the potential molecular mechanisms. In addition, we examine the regulatory mechanisms of traditional Chinese medicine on lung AQPs, and summarizes the research progress of inhibitors and small molecular compounds that modulate AQPs in lung diseases.

Implications: AQPs may serve as promising therapeutic targets for lung diseases. This review offers novel insights and a foundation for the diagnosis, treatment, and drug development of lung diseases, positioning AQPs as a potential tool in combating these conditions.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease associated with accumulation of amyloid beta peptides and intracellular neurofibrillary tangles formed by hyperphosphorylated Tau. Autophagy, an evolutionarily conserved process of self-degradation and turnover of cellular constituents, is important for normal cell growth but may be defective in diseases. A growing body of data implies that autophagy strongly affects AD pathogenesis. Autophagy mediates degradation of damaged organelles and proteins as well as neurotoxic aggregates, by regulating their clearance. Thus, impaired autophagy may account for the accumulation of protein aggregates. Since AD is characterized by neuroinflammation, impaired mitochondrial and lysosomal functions, and the accumulation of protein aggregates, the roles of autophagy/mitophagy in Alzheimer's will be extensively evaluated. In the current review, we will discuss the connection between autophagy/mitophagy and Alzheimer's. It seems that Alzheimer-related proteins such as APOE4, TREM2, PSEN1/2, APP and Tau can regulate autophagy. In turn, depending on the cellular system and animal model, autophagy regulating proteins such as Atg7, BECN1, GSK3B, MAP1LC3B, SQSTM1, TFEB and VCP can affect AD progression as discussed. We will also describe the effect of sex and lifestyle impact on autophagy and AD. Finally, we will describe how the current knowledge may contribute to potential therapeutic strategies.

Objective and design: This study was designed to delineate how Piezo1 orchestrates macrophage polarization and autophagy in psoriasis and to determine whether the PI3K/AKT axis mediates these effects.

Material or subjects: Wild-type and Piezo1-knockout C57BL/6 mice were obtained from Vital River; human THP-1 monocytes and HaCaT keratinocytes were supplied by the Cell Bank of the Chinese Academy of Sciences.

Treatment: Imiquimod was applied topically for six consecutive days; Piezo1 was silenced with shRNA, and autophagy was pharmacologically inhibited (10 mM 3-MA) or activated (200 nM rapamycin).

Methods: HE staining, immunohistochemistry and RNA-seq were performed in vivo. Western blot, immunofluorescence and flow cytometry quantified LC3-II/I, p62, PI3K/AKT proteins and CD86/CD206; cytokines were measured by ELISA.

Results: Piezo1 expression was significantly elevated in psoriatic lesions (P < 0.01). Genetic deletion of Piezo1 markedly attenuated disease severity, accompanied by an increased LC3-II/I ratio, reduced p62 accumulation, and a pronounced decline in inflammatory cytokine levels. Macrophages shifted from M1 to M2, suppressing keratinocyte proliferation and promoting apoptosis. RNA-seq confirmed the PI3K/AKT pathway as the key mediator.

Conclusions: Piezo1 amplifies cutaneous inflammation by inhibiting autophagy and activating PI3K/AKT signalling to drive M1 macrophage polarization.