International Journal of Inflammation最新文献

Hypoxia-inducible factor-2α (HIF-2α), a key regulator of cellular adaptation to hypoxia, modulates cellular metabolism, allowing cells to survive under hypoxic conditions. In immune responses, infected or inflamed tissues often exhibit hypoxia, and HIF-2α plays a vital role in helping immune cells adapt. HIF-2α also plays a dual and context-dependent role in inflammation. HIF-2α exhibits both pro- and anti-inflammatory effects in inflammation depending on cell type, disease microenvironment, and signaling pathways. This article describes how HIF-2α regulates immune cell function and its essential role in inflammation, as well as the effects of HIF-2α on the development of inflammation through different signaling pathways. Finally, it explores the potential of HIF-2α as a therapeutic target.

Introduction: Interleukin-17 (IL17) plays a crucial role in the development of psoriatic plaques, making it a valuable therapeutic target. Recently, aptamers have been identified as promising candidates for inhibiting the biological activity of biomolecules. Despite these advantages, their applications are limited due to negative charge, small size, and lower affinity compared to monoclonal antibodies. To overcome these limitations, in this study, we assessed the therapeutic effects of the gold nanoparticle (AuNPs)-conjugated anti-IL17 single-stranded DNA aptamer in the imiquimod-induced C57BL/6 psoriasis animal model.

Methods: Hydrogel-containing anti-IL17A aptamer (M2) or aptamer-conjugated AuNPs were applied topically to the dorsal skin of the C57BL/6 mice 10 min before imiquimod treatment for 5 consecutive days. Psoriasis lesions and skin tissue sections were evaluated using the modified psoriasis area severity index (PASI) score and histology. The mRNA expression levels of inflammatory factors, including IL17A, Interleukin1β (IL1β), and S100 calcium-binding protein A9 (S100A9), were assessed using reverse transcription-quantitative polymerase chain reaction.

Results: Cumulative modified PASI score, as well as IL17A, IL1β, and S100A9 mRNA expression levels, showed a significant decrease in the mice treated with anti-IL17A aptamer and anti-IL17A aptamer-conjugated AuNPs in comparison to the imiquimod group (p < 0.05). The combination of anti-IL17A aptamer with AuNPs in low concentrations (44 pmol) significantly reduced the thickness of the keratinocyte layer (p < 0.05). In accordance with these results, treatment with anti-IL17A aptamer with AuNPs improved the modified PASI score in the mice skin.

Conclusion: The findings of our study suggest that the anti-inflammatory properties of anti-IL17A (M2) aptamer are amplified when conjugated with AuNPs in the psoriasis-like model. It seems to be a promising alternative for inhibiting the antibodies of IL17.

Neutrophils, the most abundant innate immune cells, have recently emerged as central regulators in the pathogenesis and treatment of osteoporosis. Traditionally viewed as transient inflammatory responders, neutrophils are now recognized as dynamic mediators linking immune dysregulation, bone remodeling, and aging in the context of osteoimmunology. This review provides a comprehensive synthesis of their multifaceted roles in bone metabolism: promoting osteoclastogenesis via RANKL, ROS, and neutrophil extracellular traps (NETs), while concurrently inhibiting osteoblast activity through TGF-β1 and bone marrow-derived stress signals. We highlight the involvement of neutrophils in postmenopausal osteoporosis driven by estrogen deficiency and in senile osteoporosis associated with immune aging, with particular attention to pathogenic subsets such as TGF-β1⁺CCR5⁺ neutrophils. In addition, we examine the clinical relevance of neutrophil-related biomarkers, such as neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and citrullinated histone H3 (Cit-H3), for diagnosis and risk stratification, as well as emerging therapeutic strategies that target NETosis and CCR5 signaling or employ neutrophil-homing drug delivery systems. By elucidating these immune-bone interactions, neutrophils were found to be promising diagnostic biomarkers and immunotherapeutic targets in osteoporosis, paving the way for precision intervention.

Probiotics are strains of living bacteria and yeast that play an important role in regulating the gut microbiota and enhancing host immunity. In the last decade, the bacterial species Akkermansia muciniphila has attracted great interest due to its possible probiotic properties, which play an important role in human health. However, the mechanisms of action of A. muciniphila are still poorly understood. The effect of the A. muciniphila on the intestinal microbiome of model animals with systemic inflammation induced by lipopolysaccharide (LPS) is unexplored. This study aims to investigate the impact of A. muciniphila on the microbiological composition of the mouse gut under LPS-induced systemic inflammation using high-throughput sequencing. The study used a new generation sequencing method aimed at genome-wide sequencing of microorganisms, which makes it possible to study changes in the composition of the microbiome at the bacterial species level, as well as to identify the genes of the metabolic pathways of intestinal bacteria in the studied mice. Our analysis revealed statistically significant differences across all studied groups, with a notable predominance of members from the families Muribaculaceae, Rikenellaceae, and Oscillospiraceae. Consumption of A. muciniphila increased the alpha diversity of gut bacteria (Shannon index) in the context of induced inflammation. Evaluation of the effect of LPS and A. muciniphila on metabolic pathways showed statistically significant differences for the pathways of synthesis and degradation of amino acids, transforming folic acid, and synthesis of sugars. Genetic analysis showed that the probiotic bacterium A. muciniphila reduced the degree of negative effects of LPS on the mouse gut microbiome under systemic inflammation.

Background: Recent studies have provided evidence supporting the presence of a commensal joint microbiome; however, its role in the pathogenesis of spondyloarthritis (SpA) remains unclear. This study aimed to characterize the joint microbiome and assess its role in bacterial dissemination and systemic involvement.

Methods: DBA/1 mice with spontaneous arthritis (SpAD) and healthy BALB/c mice, as well as biopsies from SpA patients, were analyzed by histology (Gram staining and IHC), short-read next-generation sequencing of the 16S rRNA gene amplicons, and transcriptomics. Shared bacterial species were evaluated across tissues, including the liver and heart, and the colocalization of bacterial and inflammatory markers was assessed using double indirect immunofluorescence (IIF).

Results: Bacteria were detected in the joints of healthy and SpAD mice, with significantly greater abundance in the latter. Microbiome analysis revealed distinct bacterial communities, with genera, such as Pelomonas and Aerococcus uniquely identified in the joints of SpAD mice, indicating a state of dysbiosis. Several bacterial species, including Prevotella sp., Ruminococcus gnavus, Lactobacillus johnsonii, and Limosilactobacillus reuteri, were detected in both the gut and joints of SpAD mice. Additionally, bacterial DNA from these taxa was also amplified from liver and heart tissues, indicating systemic dissemination. Transcriptomic analysis revealed dysregulated bacterial response pathways in SpAD joints, with an inflammatory profile distinct from that observed in gut tissues. Double IIF confirmed the colocalization of bacterial components with proinflammatory cytokines in joint cells. In human SpA biopsies, Gram staining and IHC also identified bacteria in sacroiliac and tarsal tissues.

Conclusions: These findings confirm the presence of bacteria in the joints of healthy and SpAD mice, as well as SpA patients. The joint microbiome differs between healthy and diseased mice, contributing to inflammation through dysregulated bacterial responses. Additionally, the identification of shared bacterial species between the gut and joints, as well as their detection in the liver and heart, supports the hypothesis of bacterial dissemination consistent with translocation and systemic involvement.

Inflammation, pain, and fever cause discomfort and misery and lower the productivity and quality of life among the victims. The severe effects of synthetic drugs used to treat these conditions necessitate the need for alternative therapeutic agents. Strychnos henningsii is used in folkloric medicine to manage inflammation, pain, and fever, although scientific evidence to validate these claims is lacking. This study aimed to determine the in vivo anti-inflammatory, antinociceptive, and antipyretic potential of the methanol extract of S. henningsii. In the anti-inflammatory, antinociceptive, and antipyretic assays, animals (n = 5) were randomly assigned into six groups: normal control, negative control, diclofenac control, and extract-treated at 25, 50, and 100 mg/kg body weight (bw). Inflammation and pain were induced through injection of 5% formalin (50 μL) in the left hind paw, while pyrexia was induced through intraperitoneal injection of steam-distilled turpentine (20 mL/kg bw). The extract was also subjected to phytochemical screening using gas chromatography-mass spectrometry (GC-MS). The extract at the three doses significantly reduced paw edema, time spent in nociception, and rectal temperature relative to the negative control (p < 0.05), indicating anti-inflammatory, antinociceptive, and antipyretic effects, respectively. In the fourth hour, the extract at 25, 50, and 100 mg/kg bw inhibited paw edema by 4.34 ± 0.15, 6.13 ± 0.29, and 7.43 ± 0.42%, respectively. In the early and late phases, the extract at 100 mg/kg bw inhibited pain by 61.18 ± 0.75 and 66.71 ± 0.93%, respectively. In the 4th hour, the extract at 25, 50, and 100 mg/kg bw inhibited pyrexia by 1.97 ± 0.13, 2.39 ± 0.17, and 2.54 ± 0.17%, respectively. These effects were dose-dependent and were associated with phytochemicals identified using GC-MS analysis, such as terpenes, polyphenols, fatty acids, and salicylates. The study concluded that the extract possesses phytocompounds with anti-inflammatory, antinociceptive, and antipyretic potential and could be an alternative therapeutic agent against pain, inflammation, and pyrexia.

Background: Hepatic ischemia-reperfusion injury (HIRI) is one of the main causes of hepatic fibrosis that occurs during liver surgery. This study aimed to investigate the protective effect of geraniol (GNL) against HIRI in a rat model.

Methods: Wistar rats were randomly divided into seven groups and subjected to 45 min of hepatic ischemia, followed by either 60 min or 6 h of reperfusion. Immediately before reperfusion, graded doses of geraniol (50 and 100 mg/kg) were administered intraperitoneally. Serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured to evaluate liver function. Antioxidant enzyme activities were assessed in liver homogenates. The concentrations of TNF-α, IL-1β, Bax, and Bcl2 mRNA and proteins in liver tissue were measured using RT-PCR and enzyme-linked immunosorbent assay (ELISA). The expression of Bcl2 and caspase-3 in liver tissue was evaluated by immunohistochemistry. In addition, liver tissue histopathology was examined under a light microscope.

Results: The results demonstrated that liver damage significantly increased after repeated HIRI. However, treatment with GNL reduced hepatic enzyme levels and mitigated pathological changes resulting from repeated HIRI. Additionally, GNL treatment led to a decrease in apoptotic factors.

Conclusion: GNL may be a potential therapeutic agent for preventing or treating hepatic fibrosis caused by ischemia-reperfusion injury.

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Inflammation, as the main pathophysiological mechanism, runs through the whole course of sepsis. Notably, P2X receptors have the capacity to mediate inflammation, nerve signaling, and thrombosis, which underscores their pivotal role in the progression of sepsis. The goal of this study is to review the specific role of the P2X family in the pathogenesis of sepsis in various organs in light of currently available evidence.

When presenting the role of platelets in immunity, the organelles and processes occurring within them are listed, and due to their lack of a cell nucleus, their specific transcriptional activity is discussed. Their formation, activation, and functional activity are also described, along with the characterization of elements important for shaping their intravascular activity, including immunity, such as their granules and extracellular vesicles (EVs). Presenting platelets in the context of their immune role, it is indicated that their activation and activity are complex processes resulting from the binding of their receptors with the endothelium of blood vessels, pattern recognition receptors (PRRs) of immune system cells, pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), and lifestyle-associated molecular patterns (LAMPs). As a result of these interactions, the inflammatory phenotype of platelets is promoted, making them not only the fundamental elements of homeostasis in blood vessels but also, above all, of immunity. Discussing the immunological role of platelets in blood vessels, biologically active substances contained in their five types of granules (α, δ, lysosomes, peroxisomes, and T), and two subtypes of EVs (exosomes and ectosomes-microvesicles) that determine their activity, including the immunological status, are characterized. Moreover, describing the role of platelets in blood vessels, it has been demonstrated that these cells are not only effective sentinels and regulators of these vessels, as previously assumed, but also exhibit strong pro- and anti-inflammatory, immunomodulatory, and regenerative effects, making them fundamental cellular elements determining intravascular immunity. It is also pointed out that by inducing an inflammatory environment in blood vessels, platelets can not only cause potential tissue damage but also emerge as potential cellular candidates for treating inflammatory diseases.

Background: The role of the inflammatory microenvironment in initiating and progressing chronic lymphocytic leukemia (CLL) is still not clarified. To date, it has been shown that the only way to reflect inflammation in the systemic circulation is to assess inflammatory markers in peripheral blood. However, in the age of modern technology, a more detailed analysis of inflammatory cells circulating in the blood of CLL patients would be useful. Objectives: The study aimed to evaluate the relationship between one of the hematological inflammatory indexes-the monocyte/lymphocyte ratio (MLR) and the risk of CLL progression associated with disease activity. In addition, we wanted to analyze whether the MLR parameter in CLL could suggest the functional immune status of circulating main monocyte subsets. Methods: The study included peripheral blood samples from 54 untreated, newly diagnosed CLL patients and 20 healthy volunteers (HVs). Immunological characterization of monocyte subpopulations included their detailed assessment by multiparametric flow cytometry, including evaluation of surface markers and intracellular expression of cytokines. In addition, the relative expression of selected microRNA (miR-21-3p, miR-150-5p, miR-106a-5p) was determined in FACS-sorted monocyte subsets. Results: In our study, CLL patients had significantly lower values of MLR parameters compared to HVs (p < 0.0001). However, the value of MLR was higher in CLL patients with negative clinical and laboratory prognostic factors, i.e., increased percentage of CD5+/CD19+ cells with ZAP-70 and CD38 expression. We noticed that the percentage of intermediate monocytes is significantly higher, but classical and nonclassical ones are significantly lower in MLR-high compared to MLR-low CLL patients. Moreover, among the monocyte subsets circulating in the blood of MLR-high, ZAP-70+, and CD38+, CLL patients' intermediate monocytes were characterised by increased intracellular expression of IL-10 and decreased miR-150-5p relative expression compared to intermediate monocytes in the MLR-low, ZAP-70-, and CD38- groups, suggesting a potential link between hematological inflammatory index and the formation of intermediate monocytes that promote CLL burden. Conclusions: The MLR index may serve not only as a marker of CLL activity, but also indirectly indicate changes in the phenotype and function of monocyte subpopulations present in the blood microenvironment. Moreover, the MLR-high parameter seems to correspond to an increase in the percentage of intermediate monocytes with anti-inflammatory properties, which may potentially promote disease progression and worsen its prognosis.