Iranian journal of allergy, asthma, and immunology最新文献

Lipopolysaccharide (LPS)-induced inflammation in macrophages involves complex signaling pathways. This investigation explored the regulatory roles of triggering receptor expressed on myeloid cells-1 (TREM1) and interleukin (IL)-26 in the Janus kinase/signal transducer and activator of transcription (JAK/STAT) and nuclear factor-kappa B (NF-κB) p65 pathways in LPS-stimulated RAW 264.7 macrophages. RAW 264.7 cells were treated with LPS to assess TREM1 expression. TREM1 or IL-26 was silenced using short hairpin RNA (shRNA), while IL-26 was overexpressed via plasmid transfection. The JAK2 inhibitor AG490 was used to block JAK/STAT signaling. Western blot, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and enzyme-linked immunosorbent assay (ELISA) were employed to analyze the protein and mRNA levels of inflammatory markers and signaling molecules. Results showed that LPS upregulated TREM1 expression. In addition, TREM1 knockdown suppressed p65 activation and reduced inflammatory cytokine levels. Moreover, silencing TREM1 inhibited IL-26 and JAK/STAT phosphorylation (p-JAK1, p-JAK2, p-STAT1, and p-STAT3). Similarly, IL-26 knockdown or AG490 treatment attenuated p65 activation and inflammation. Furthermore, IL-26 overexpression reversed the anti-inflammatory effects of TREM1 silencing. Overall, TREM1 promoted LPS-induced macrophage inflammation via IL-26-mediated JAK/STAT and NF-κB pathway activation, suggesting that TREM1 and IL-26 are potential therapeutic targets.

TC-1 is a recognized cancer cell line derived from lung epithelial cells that have been altered using the oncogenic E6 and E7 genes of human papillomavirus (HPV). These TC-1 cells are frequently utilized in preclinical research focused on lung cancer and HPV-associated tumors. The incidence of lung cancer and HPV-related cancers is significantly increasing. Drug resistance and the lack of selectivity in current treatments reduce their effectiveness. Researchers are seeking new therapeutic methods, including targeted therapies, immunotherapy, and oncolytic virus and bacterial therapies, to improve treatment outcomes and decrease mortality associated with these diseases. In this context, the present original study aimed to evaluate the potency of wild-type Newcastle disease virus (NDV-WTS) on lactate dehydrogenase (LDH) secretion and the induction of apoptosis in TC-1 cells. In this experimental study, the TC-1 cell lines were cultured under laboratory conditions. Subsequently, they were treated with different multiplicities of infection (MOIs) of NDV-WTS (1, 2, and 4). Finally, the oncolytic effects of the virus were evaluated using laboratory assays, including MTT (cell viability), reactive oxygen species (ROS), LDH, survival rates, and the activities of Caspases 8 and 9. The results indicated that NDV-WTS significantly decreased cell viability while increasing apoptosis, ROS levels, LDH release, and Caspase 8 and 9 activities compared to the control group. Molecular analyses further revealed that treatment of TC-1 cells with NDV significantly increased the expression of Bax, Casp8, and Casp9, while significantly decreasing Bcl2 expression relative to the control group. NDV-WTS demonstrated remarkable efficacy in treating lung cancer and HPV-associated tumors. Based on the results of the present study, the use of Newcastle disease virus in the treatment of lung cancer and HPV-associated tumors may be beneficial, which requires further studies and clinical trials.

Adenosine deaminase 2 (ADA2) deficiency is an autosomal recessive disease with varying degrees of clinical phenotypes and disease severity. The phenotypic spectrum of the disorder has expanded from vasculitis with stroke to include pure red cell aplasia, bone marrow failure, autoimmune cytopenia, lymphoproliferation, and variable degrees of immunodeficiency. Here, we describe two cases of ADA2 deficiency: one presented with an early-onset stroke that resembled an early-onset polyarteritis nodosa (PAN), and the other as an adult-onset vasculitis that progressed to severe neutropenia with recurrent infection and lymphoproliferation. Patient 1, a 10-year-old male, had a reported pathogenic ADA2 homozygote variant; c.139G˃C (p.Gly47Arg), and patient 2, a 34-year-old male, had a reported likely pathogenic homozygous ADA2 variant; c.578C>T (p.Pro193Lys). Our second patient was the first DADA2 patient who showed that DADA2 is not a static disease and can progress from vasculitis to bone marrow failure in the course of the disease. Therefore, the previous recommendation introducing anti-TNF-α as a preferred treatment for vasculitis manifestations and hematopoietic stem cell transplantation as the preferred treatment for bone marrow failure can no longer apply. We should consider HSCT for DADA2 patients from the very beginning. The Physician has to be aware of this monogenic disorder's varied presentation and multi-organ involvement. Early recognition and proper treatment are crucial for this potentially fatal disease.

Premature infants with immature gastrointestinal tracts rely on parenteral nutrition (PN) to meet nutritional and energy requirements for growth. In this study, we compared the nutrition-related immune status of premature infants receiving SMOF emulsions (multiple oil-fat emulsions) versus those receiving MCT/LCT emulsions (medium-/long-chain triglyceride emulsions) at different times during PN, and we analyzed the relationship between immune function and clinical outcomes. Sixty premature infants from Dongxihu District People's Hospital, recruited between September 2023 and September 2024, were divided into an observation group and a control group. The observation group received SMOF emulsions, while the control group received MCT/LCT-containing emulsions. We compared immune function, clinical outcomes, and complications between the two groups at different PN timings. The effects of fat-emulsion type on immune indices and their relationship with clinical outcomes were assessed using logistic regression and ROC analysis. The clinical data of the preterm infants in both groups were similar. Immune function and clinical outcomes were better in the observation group than in the control group, and the complication rate was lower. Logistic and ROC analyses revealed that the type of fat emulsion was closely related to immune indices, and these immune indices were highly correlated with clinical outcomes. Both interventions improved immunity in preterm infants, with better results in the observation group than in the control group. The use of SMOF emulsions was superior to MCT/LCT-containing emulsions in preterm infants requiring long-term PN, and this immune improvement significantly optimizes clinical outcomes.

Adenovirus infection is a common cause of pediatric respiratory disease, often misdiagnosed as a bacterial infection. This study compared immune-inflammatory markers in children with adenovirus- vs bacterial-induced suppurative tonsillitis and evaluated their correlation with adenovirus pneumonia. A retrospective study of 275 children (145 with adenovirus, 130 with bacterial infections) admitted to The First People's Hospital of Changde, China (January-June 2019), was conducted. Laboratory markers (white blood cell [WBC] count, C-reactive protein [CRP], serum amyloid A [SAA], procalcitonin [PCT], heparin-binding protein [HBP], tumor necrosis factor-alpha [TNF-α], and interleukin 6 [IL-6]) were analyzed. Adenovirus cases were stratified by pneumonia status (58 with pneumonia, 87 without pneumonia) via chest computed tomography. Compared with the bacterial group, the adenovirus group had lower WBC counts (14.97 [1.37] vs 18.86 [2.65] ×109/L), CRP levels (15.26 [3.44] vs 26.36 [3.18] mg/L), and PCT levels (15.06 [2.12] vs 42.53 [4.58] ng/L) but higher SAA levels (216.75 [39.23] vs 136.55 [28.66] mg/L). Among children with adenovirus, those with pneumonia had elevated SAA (236.39 [38.67] vs 203.65 [33.95] mg/L), HBP (44.30 [8.93] vs 35.62 [6.77] ng/mL), TNF-α (731.52 [99.21] vs 604.21 [95.53] ng/L), and IL-6 (96.86 [17.63] vs 76.55 [15.50] ng/L) levels. A combination of SAA, HBP, TNF-α, and IL-6 predicted pneumonia with an area under the curve of 0.927 (sensitivity, 87.93%; specificity, 88.51%). SAA, HBP, TNF-α, and IL-6 are strongly associated with adenovirus pneumonia, and their combined measurement improves diagnostic accuracy.

The risks associated with in vivo tests in the diagnosis of immediate drug hypersensitivities result in evaluating alternative in vitro tests, such as the Basophil Activation Test (BAT). This pilot study aimed to set up a BAT and compare it with a specific Immunoglobulin E (sIgE) assay for penicillin G and Ibuprofen in patients with immediate hypersensitivity to β-lactams or nonsteroidal anti-inflammatory drugs (NSAIDs). Eleven subjects with a clear history of immediate hypersensitivity to one of the β-lactams (n=5), the NSAIDs (n=3), or both (n=3) entered this study. BAT and sIgE assays were performed regarding the patient's history. The most frequent manifestations were angioedema, shortness of breath, urticaria, and nausea. Eight patients had anaphylactic reactions. The results presented a positive BAT for penicillin G and one for Ibuprofen. Moreover, three patients with a history of the β-lactams reaction demonstrated positive sIgE to β-lactams in the ImmunoCAP. Despite a lack of agreement between the positive results of the BAT and sIgE assay, five patients were identified by one of these methods. Despite positive BAT and sIgE results in two and three patients, respectively, the risks, high cost, and time-consuming nature of drug challenges render these tests valuable for reducing the number of patients who are candidates for a drug challenge.

Spinal cord injuries (SCI) lead to complex primary and secondary damage that disrupts neural function. Current treatments are often insufficient and unable to fully repair spinal cord injuries, highlighting the urgent need for new medicines and innovative therapies. This study aimed to evaluate the therapeutic potential of abscisic acid (ABA) in SCI by examining its effects on immune-inflammatory genes' expression in rats. This phytohormone possesses anti-inflammatory and neuroprotective properties, rendering it a potential agent for reducing secondary damage following spinal cord injury. Additionally, we performed protein-protein interaction (PPI), pathway enrichment, functional annotation, and gene ontology (GO) analyses to gain a comprehensive understanding of the functions of the affected genes. Based on the results, SCI led to changes in the expression of immune/inflammation-related genes in rats. However, the administration of ABA alleviated the effects. ABA downregulated proinflammatory genes (IL-6, IL-1β, MCP, TLR2, TLR4) and neural signaling components (NMDA, AMPA, NK1R), while upregulating adrenergic receptors (ADRA1A, ADRB1) and a gamma-aminobutyric acid receptor (AGBRA2). PPI analysis identified FOS, IL-1β, IL-6, MMP9, and TLR4 as crucial nodes in the network, exhibiting the highest degree of interaction. Functional analyses revealed potential impacts on cellular responses, metabolic processes, and synapse-associated extracellular matrix components. Notably, these genes were enriched in inflammatory signaling pathways according to KEGG analysis. These findings suggest that ABA has a significant modulatory effect on gene expression following SCI, particularly in reducing inflammation and immune responses, thereby highlighting its potential as a novel therapeutic agent for SCI.

This study aims to investigate the role of notopterol in alleviating endometritis induced by lipopolysaccharide (LPS) and to explore its underlying mechanisms.Human endometrial epithelial cells (hEECs) were treated with LPS to establish an in vitro model of endometritis, and the cells were divided into five groups: control, LPS, LPS+notopterol(15 mol/L), LPS+notopterol(305 mol/L) and LPS+notopterol(45 mol/L) groups. The expression levels of inflammatory factors were determined by Enzyme-Linked ImmunoSorbent Assay (ELISA). Apoptosis was detected by TdT-mediated dUTP Nick-End Labeling (TUNEL) method. Cell viability was determined by Cell Counting Kit-8 (CCK-8) test. Western blot was used to detect the expression levels of nuclear factor κB(NF-κB) p65, NF-κB inhibitor (IκBα), p-NF-κB p65 and p-IκBα. Following LPS treatment, cytokine levels significantly increased compared to the control group.; moreover, cell proliferation decreased, apoptosis increased, and the expression level of p-NF-κB p65 was increased. Subsequently, the LPS-treated hEECs were exposed to notopterygium. Compared to the LPS group. Treatment with LPS + notopterol resulted in a dose-dependent reduction in inflammatory cytokines, increased cell proliferation, and a significant reduction in apoptosis. Furthermore, the expression levels of p-NF-κB p65 and p-IκBα were downregulated. These findings suggest that notopterol alleviates LPS-induced endometritis by inhibiting the TLR4/NF-κB signaling pathway.

Idiopathic pulmonary fibrosis (IPF) is a severe lung disease with a poor prognosis, characterized by immune cell activation. The role of T helper (Th) cell transcription factors in IPF pathogenesis remains unclear. In this study, we investigated Th cell transcription factors and related cytokines in IPF patients. Twelve IPF patients and eight healthy controls (HC) were enrolled in this pilot study. Serum levels of fibrosis-associated mediators (Interferon-inducible protein 10 (IP-10), tumor necrosis factor-α (TNF-α), tumor growth factor-β (TGF-β), CXCL-8, interferon-γ (IFN-γ)) were measured by enzyme-linked immunosorbent assay (ELISA). Flow cytometry assessed Th transcription factors T box transcription factor (T-bet,), GATA-binding protein 3 (GATA-3), Retinoic acid-related orphan recepto (ROR-γt), forkhead box P3 (FOXP3)) and intracellular cytokines (IL-4, IL-17). SerumTGF-β, CXCL-8, TNF-α, and IFN-γ were significantly elevated, while IP-10 (pT-bet, GATA3, ROR-γt, or FOXP3 were observed. Positive correlations were found between T-bet and GATA3, IL-4, ROR-γt, and TNF-α expression with age, while FOXP3 expression negatively correlated with age. T-cell transcription factors were unchanged in IPF despite changes in inflammatory protein expression. Reduced IP-10 may serve as a potential marker.

Liver fibrosis is known as a condition characterized by chronic inflammation and excessive extracellular matrix deposition that causes cirrhosis and liver failure. Stem cell therapy is a promising strategy for the management of liver fibrosis because it not only improves tissue regeneration but also modulates by immunomodulatory mechanisms. This systematic review aimed to evaluate the immunoregulatory effects of stem cells in both experimental models and clinical studies of liver fibrosis. A total of 29 studies were included, comprising several stem cell sources, including bone marrow-derived mesenchymal stem cells (BM-MSCs), umbilical cord-derived MSCs (UC-MSCs), adipose tissue-derived MSCs (AT-MSCs), and stem cells from human exfoliated deciduous teeth (SHED), among others. Studies reported that stem cells could decrease proinflammatory cytokines (e.g., TNF-α, IFN-γ, IL-17) and fibrosis-related markers, while increasing levels of anti-inflammatory cytokines (e.g., IL-10, IL-4) and regulatory immune cells such as Tregs (regulatory T cells). Stem cells could affect immune homeostasis via modulating in macrophage polarization, T cell subsets, and B cell activity, resulting in attenuated fibrotic progression and improved liver function. Despite variability in cell types, routes of administration, and fibrosis models, the results support the potential of stem cell therapy to reform the hepatic immune microenvironment. However, more standardized protocols and clinical validations are required. This study emphasizes the immunomodulatory potential of stem cells as a therapeutic method in liver fibrosis. It brings a clear view into their mechanisms of action and the foundation for future translational applications.