{"title":"The imbalance of circulating PD-L1-expressing non-classical/ classical monocytes is involved in immunocompromised host related pulmonary opportunistic infection.","authors":"Danhong Zhou, Yujia Jin, Yifan Jin, Yu Shen, Qiuxia Qu, Cheng Chen","doi":"10.1177/17534259251316152","DOIUrl":"https://doi.org/10.1177/17534259251316152","url":null,"abstract":"<p><p>The application of biological therapy and glucocorticoids in Auto-immune diseases (AID) patients will cause immunocompromised host (ICH) prone to infection. And monocytes play a key role in both innate and adaptive immune responses. We aimed to investigate the changes of circulating monocyte subsets in AID or AID-ICH patients with pulmonary infection. The subgroups and PD-L1 expression of monocytes were measured by flow cytometry in healthy individuals (HC), new-onset AID patients (AID cohort) and AID-ICH patients with pulmonary opportunistic infection (AID-ICH cohort). Flow cytometry analysis was used to determine the distribution of monocyte subsets, including classical monocytes (CL, CD14<sup>++</sup>CD16<sup>-</sup>), intermediate monocytes (ITM, CD14<sup>++</sup>CD16<sup>+</sup>) and non-classical monocytes (NC, CD14<sup>+/-</sup>CD16<sup>++</sup>), as well as the dynamic change of PD-L1 <sup>+ </sup>cluster among monocyte subsets. Among total monocyte, AID-ICH displayed decreased CL subset along with increased NC subset compared to HCs and AID. Regarding PD-L1 <sup>+ </sup>monocytes, although CL subset constituted the majority of that in HCs, AIDs and AID-ICHs, imbalance of NC/CL within PD-L1 <sup>+ </sup>monocytes was only noticed in AID-ICHs (<i>P</i> < 0.05). Furthermore, when AID subjects were developed into immunocompromised status (ICH), PD-L1 <sup>+ </sup>cluster in CL was minorly decreased (<i>P</i> > 0.05). Clinically, the lower ratio of PD-L1 <sup>+ </sup>cluster among CL subset (<i>P</i> < 0.05) and the less differentiated CL in PD-L1 <sup>+ </sup>monocytes (<i>P</i> < 0.05) was more likely to leaded to disease progression. The imbalance of circulating NC/CL subset was remarkable in immunocompromised host with pulmonary opportunistic infection, especially involvement of PD-L1<sup>+</sup> cluster, which served as a potential biomarker in clinical practice.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"31 ","pages":"17534259251316152"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Innate ImmunityPub Date : 2025-01-01DOI: 10.1177/17534259251314774
Jameel Al-Tamimi, Suliman Alomar, Ali Aljuaimlani, Lamjed Mansour
{"title":"Association of killer immunoglobulin-like receptor genotypes and haplotypes with acute lymphoblastic leukemia risk.","authors":"Jameel Al-Tamimi, Suliman Alomar, Ali Aljuaimlani, Lamjed Mansour","doi":"10.1177/17534259251314774","DOIUrl":"https://doi.org/10.1177/17534259251314774","url":null,"abstract":"<p><strong>Background: </strong>Killer immunoglobulin-like receptors (KIRs) are key molecules used by natural killer (NK) cells to interact with target cells. These receptors exhibit extensive genotypic polymorphism which has been associated with varying outcomes in immune responses against diseases. This study aimed to investigate the relationships between <i>KIR</i> genotypes and haplotypes with acute lymphoblastic leukemia (ALL) in Saudi patients.</p><p><strong>Methods: </strong>A total of 259 Saudi subjects including 145 cases of acute lymphoblastic leukemia (ALL) and 114 healthy controls living in Riyadh were genotyped for 16 <i>KIR</i> genes and the two <i>HLA-C1</i> and <i>-C2</i> allotypes using PCR-SSP genotyping method.</p><p><strong>Results: </strong>A significant high frequency of the two inhibitory <i>KIR</i> genes; <i>2DL1</i> (OR = 2.4; <i>p</i> < 0.0001) and <i>3DL1</i>(OR = 10.87; <i>p</i> = 0.0068) in ALL compared to healthy group was observed. In contrast, the activating <i>2DS4</i> gene was significantly higher in healthy controls (OR = 0.15, <i>p</i> < 0.0001) compared to ALL patients. Haplotype analysis shows that BX haplogroup was strongly associated with the occurrence of ALL (OR = 4.39; <i>p</i> < 0.0001). Further combinatory analysis of <i>KIR</i> genes with their <i>HLA-C1</i> and <i>-C2</i> ligands demonstrated strong statistically protective effect of the <i>2DS1-C2</i> combination from ALL (OR = 0.06; <i>p</i> = 0.0003).</p><p><strong>Conclusion: </strong>This study presents strong evidence supporting the connection between certain <i>KIR</i> genotypes, haplotypes, and <i>KIR-HLA</i> combinations with acute ALL in the Saudi population. The heightened occurrence of inhibitory <i>KIR</i> genes (<i>2DL1</i> and <i>3DL1</i>) and the BX haplotype in ALL patients indicates a possible involvement of these genetic variability with the dysfunctional of NK cells in the context of ALL disease.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"31 ","pages":"17534259251314774"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Innate ImmunityPub Date : 2024-12-23DOI: 10.1177/17534259241306237
Hee Young Cho, Kyo Hoon Park, Eunji Oh, Min Jung Lee, Bo Young Choi, Eun Mi Im
{"title":"Plasma acute phase proteins as potential predictors of intra-amniotic inflammation and infection in preterm premature rupture of membranes.","authors":"Hee Young Cho, Kyo Hoon Park, Eunji Oh, Min Jung Lee, Bo Young Choi, Eun Mi Im","doi":"10.1177/17534259241306237","DOIUrl":"10.1177/17534259241306237","url":null,"abstract":"<p><strong>Background: </strong>We aimed to investigate the potential of altered levels of various acute phase proteins (APPs) in the plasma, either used alone or in combination with ultrasound-, clinical-, and conventional blood-based tests, for predicting the risk of intra-amniotic inflammation (IAI), microbial invasion of the amniotic cavity (MIAC), histologic chorioamnionitis (HCA), and funisitis in women with preterm premature rupture of membranes (PPROM).</p><p><strong>Methods: </strong>A total of 195 consecutive pregnancies involving singleton women with PPROM (at 23 + 0-34 + 0 weeks) who underwent amniocentesis and from whom plasma samples were obtained at amniocentesis were retrospectively included in this study. Amniotic fluid (AF) was cultured to assess the MIAC and analyzed for interleukin (IL)-6 levels to define IAI (AF IL-6 level of ≥2.6 ng/mL). The plasma concentrations of hepcidin, mannose-binding lectin (MBL), pentraxin-2, retinol-binding protein 4 (RBP4), serum amyloid A1 (SAA1), and serpin A1 were determined using ELISA. Ultrasonographic cervical length (CL), neutrophil-to-lymphocyte ratio (NLR), and C-reactive protein levels were measured. IAI/MIAC was defined as IAI, MIAC, or both.</p><p><strong>Results: </strong>Multivariate logistic regression analyses showed the following: (1) elevated plasma levels of hepcidin and SAA1 and decreased levels of RBP4 in the plasma were independently associated with IAI/MIAC and (2) decreased plasma RBP4 levels were independently associated with funisitis; however, (3) none of the plasma APPs investigated were associated with acute HCA when adjusted for baseline covariates. Using stepwise regression analysis, noninvasive prediction models comprising plasma RBP4 levels, CL, NLR, and gestational age at sampling were proposed, which provided a good prediction of IAI/MIAC and funisitis (area under the curve: 0.80 and 0.72, respectively).</p><p><strong>Conclusions: </strong>Hepcidin, RBP4, and SAA1 were identified as potential APP biomarkers in the plasma predictive of IAI/MIAC or funisitis in patients with PPROM. In particular, combination of these APP biomarkers with ultrasound-, clinical-, and conventional blood-based markers can significantly support the diagnosis of IAI/MIAC and funisitis.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":" ","pages":"17534259241306237"},"PeriodicalIF":2.8,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Innate ImmunityPub Date : 2024-12-23DOI: 10.1177/17534259241308661
Rasha Ahmed Ghorab, Shaimaa H Fouad, Ahmed F Sherief, Rana M Taha, Marwa Hamdy, Mohammad M Darwish, Eman M El-Sehsah, Sara I Taha
{"title":"Circulating MiR-126 as a potential biomarker in Egyptian colorectal cancer patients: A case-control study.","authors":"Rasha Ahmed Ghorab, Shaimaa H Fouad, Ahmed F Sherief, Rana M Taha, Marwa Hamdy, Mohammad M Darwish, Eman M El-Sehsah, Sara I Taha","doi":"10.1177/17534259241308661","DOIUrl":"10.1177/17534259241308661","url":null,"abstract":"<p><strong>Background: </strong>Globally, colorectal cancer (CRC) is among the most prevalent malignant tumors. It is characterized by unlimited proliferation, invasion, and metastasis. MicroRNA-126 (miR-126) has been shown in many studies to play a significant role in CRC, but data regarding its role in CRC Egyptian patients are limited.</p><p><strong>Objectives: </strong>This case-control study aimed to investigate the miR-126 as a potential marker in CRC Egyptian patients and to correlate its expression levels with CRC tumor, node, metastasis (TNM) stage, distant metastasis, and tumor size.</p><p><strong>Methods: </strong>The study included 50 adult Egyptian participants (30 patients with CRC, 10 patients with colorectal adenoma as a pathological control, and 10 healthy controls). MiR-126 expression levels were detected using Real-Time Quantitative PCR (qPCR) along with the endogenous reference gene hsa-miR-103a in all participants.</p><p><strong>Results: </strong>MiR-126 expression was significantly decreased in CRC patients than both control groups. It was associated with advanced TNM stage (<i>p </i>= 0.001) and distant metastasis (<i>p </i>= 0.002). However, it was not correlated with tumor size (<i>p </i>= 0.980), carcinoembryonic antigen (CEA) (<i>p </i>= 0.397), and cancer antigen 19-9 (CA19-9) (<i>p </i>= 0.236). The best cut-off point of miR-126 to discriminate CRC from both controls was 0.7 and to discriminate metastatic CRC from non-metastatic CRC was 0.3.</p><p><strong>Conclusions: </strong>Our results suggest that miR-126 could be used as an early marker for CRC detection among Egyptian patients and a good prognostic indicator associated with metastasis.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":" ","pages":"17534259241308661"},"PeriodicalIF":2.8,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Innate ImmunityPub Date : 2024-09-10DOI: 10.1177/17534259241269724
Suzanne M. Hurst, David A. L. Flossdorf, Raveen Koralagamage Don, Anton Pernthaner
{"title":"Selective IgG binding to the LPS glycolipid core found in bovine colostrum, or milk, during Escherichia coli mastitis influences endotoxin function","authors":"Suzanne M. Hurst, David A. L. Flossdorf, Raveen Koralagamage Don, Anton Pernthaner","doi":"10.1177/17534259241269724","DOIUrl":"https://doi.org/10.1177/17534259241269724","url":null,"abstract":"The dynamic interplay between intramammary IgG, formation of antigen-IgG complexes and effector immune cell function is essential for immune homeostasis within the bovine mammary gland. We explore how changes in the recognition and binding of anti-LPS IgG to the glycolipid “functional” core in milk from healthy or clinically diagnosed Escherichia coli (E. coli) mastitis cows’ controls endotoxin function. In colostrum, we found a varied anti-LPS IgG repertoire and novel soluble LPS/IgG complexes with direct IgG binding to the LPS glycolipid core. These soluble complexes, absent in milk from healthy lactating cows, were evident in cows diagnosed with E. coli mastitis and correlated with endotoxin-driven inflammation. E. coli mastitis milk displayed a proportional reduction in anti-LPS glycolipid core IgG compared to colostrum. Milk IgG extracts showed that only colostrum IgG attenuated LPS induced endotoxin activity. Furthermore, LPS-stimulated reactive oxygen species (ROS) in milk granulocytes was only suppressed by colostrum IgG, while IgG extracts of neither colostrum nor E. coli mastitis milk influenced N-formylmethionine-leucyl-phenylalanine (fMLP)-stimulated ROS in LPS primed granulocytes. Our findings support bovine intramammary IgG diversity in health and in response to E. coli infection generate milk anti-LPS IgG repertoires that coordinate appropriate LPS innate-adaptive immune responses essential for animal health.","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"8 1","pages":"96-118"},"PeriodicalIF":3.2,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142186183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Innate ImmunityPub Date : 2024-08-01Epub Date: 2024-11-20DOI: 10.1177/17534259241296630
Marie-Christine Bartens, Sam Willcocks, Dirk Werling, Amanda J Gibson
{"title":"Respiratory bioenergetics is enhanced in human, but not bovine macrophages after exposure to <i>M. bovis</i> PPD: Exploratory insights into overall similar Cellular Metabolic Profiles.","authors":"Marie-Christine Bartens, Sam Willcocks, Dirk Werling, Amanda J Gibson","doi":"10.1177/17534259241296630","DOIUrl":"10.1177/17534259241296630","url":null,"abstract":"<p><p>The role of macrophage (MØ) cellular metabolism and reprogramming during TB infection is of great interest due to the influence of <i>Mycobacterium</i> spp. on MØ bioenergetics. Recent studies have shown that <i>M. tuberculosis</i> induces a TLR2-dependent shift towards aerobic glycolysis, comparable to the established LPS induced pro-inflammatory M1 MØ polarisation. Distinct differences in the metabolic profile of murine and human MØ indicates species-specific differences in bioenergetics. So far, studies examining the metabolic potential of bovine MØ are lacking, thus the basic bioenergetics of bovine and human MØ were explored in response to a variety of innate immune stimuli. Cellular energy metabolism kinetics were measured concurrently for both species on a Seahorse XFe96 platform to generate bioenergetic profiles for the response to the bona-fide TLR2 and TLR4 ligands, FSL-1 and LPS respectively. Despite previous reports of species-specific differences in TLR signalling and cytokine production between human and bovine MØ, we observed similar respiratory profiles for both species. Basal respiration remained constant between stimulated MØ and controls, whereas addition of TLR ligands induced increased glycolysis, as measured by the surrogate parameter ECAR. In contrast to MØ stimulation with <i>M. tuberculosis</i> PPD, another TLR2 ligand, <i>M. bovis</i> PPD treatment significantly enhanced basal respiration rates and glycolysis only in human MØ. Respiratory profiling further revealed significant elevation of ATP-linked OCR and maximal respiration suggesting a strong OXPHOS activation upon <i>M. bovis</i> PPD stimulation in human MØ. Our results provide an exploratory set of data elucidating the basic respiratory profile of bovine vs. human MØ that will not only lay the foundation for future studies to investigate host-tropism of the <i>M. tuberculosis</i> complex but may explain inflammatory differences observed for other zoonotic diseases.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":" ","pages":"136-149"},"PeriodicalIF":2.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11577332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Innate lymphoid cells and infectious diseases.","authors":"Ting Yuan, Qianhui Zhou, Yuqiu Tian, Yangjing Ou, YunZhu Long, YingZheng Tan","doi":"10.1177/17534259241287311","DOIUrl":"10.1177/17534259241287311","url":null,"abstract":"<p><p>Innate lymphoid cells (ILCs) are the main resident lymphocytes that mostly reside in tissues owing to the lack of adaptive antigen receptors. These cells are involved in early anti-infective immunity, antitumour immunity, regulation of tissue inflammation, and maintenance of homeostasis in the internal environment of tissues and have been referred to as the \"first armies stationed in the human body\". ILCs are widely distributed in the lungs, colon, lymph nodes, oral mucosa and even embryonic tissues. Due to the advantage of their distribution location, they are often among the first cells to come into contact with pathogens.Relevant studies have demonstrated that ILCs play an early role in the defence against a variety of pathogenic microorganisms, including bacteria, viruses, fungi and helminths, before they intervene in the adaptive immune system. ILCs can initiate a rapid, nonspecific response against pathogens prior to the initiation of an adaptive immune response and can generate a protective immune response against specific pathogens, secreting different effectors to play a role.There is growing evidence that ILCs play an important role in host control of infectious diseases. In this paper, we summarize and discuss the current known infectious diseases in which ILCs are involved and ILC contribution to the defence against infectious diseases. Further insights into the mechanisms of ILCs action in different infectious diseases will be useful in facilitating the development of therapeutic strategies for early control of infections.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":" ","pages":"120-135"},"PeriodicalIF":2.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11556573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Innate ImmunityPub Date : 2024-07-01Epub Date: 2024-08-02DOI: 10.1177/17534259241269674
Sara I Taha, Hala Ghareeb Mohamed, Rasha Mamdouh, Nada E Kamal, Shaimaa Sayed Khater
{"title":"A pilot study of monocytes in relapsing remitting multiple sclerosis: Correlation with disease activity.","authors":"Sara I Taha, Hala Ghareeb Mohamed, Rasha Mamdouh, Nada E Kamal, Shaimaa Sayed Khater","doi":"10.1177/17534259241269674","DOIUrl":"10.1177/17534259241269674","url":null,"abstract":"<p><p><b>Background:</b> Numerous immune cells are involved in developing multiple sclerosis (MS). Monocytes are believed to be the first to enter the brain and initiate inflammation. The role of monocyte subtypes in MS needs to be better understood. Objective: The current study aims to investigate the presence of different subsets of monocytes in relapsing-remitting MS (RRMS) Egyptian patients and their correlation with disease activity. <b>Methods:</b> This study included 44 RRMS patients (22 patients in relapse, 22 patients in remission), diagnosed according to the 2017 MacDonalds criteria, and 44 matched healthy controls. Personal and medical histories were taken from the patients, and the Expanded Disability Status Scale (EDSS) was used to evaluate the degree of impairment. Characterization of peripheral blood monocyte subsets was done by flow cytometry for all participants. <b>Results:</b> The percentage of classical, intermediate, and non-classical monocyte subsets showed a significant increase in RRMS patients than controls with <i>p</i>-values of 0.029, 0.049, and 0.043, respectively. In the RRMS patients, there were no statistically significant correlations (<i>p</i>-values >0.05) between the EDSS scores, the duration of disease, and number of relapses in the past year and the percentages of the various monocyte subsets. Furthermore, there were no significant differences in the percentage of each monocyte subset between RRMS patients in remission and those experiencing a relapse (<i>p</i>-values >0.05). However, patients with evidence of activity in magnetic resonance imaging (MRI) had a significantly high percentage of non-classical monocytes with a <i>p</i>-value of 0.002. <b>Conclusion:</b> In RRMS patients, the three monocyte subsets (classical, non-classical and intermediate) increase significantly regardless of the disease activity. This increase denotes the vital role of monocytes and innate immunity in MS pathology, especially the non-classical monocyte subset. These findings suggest that monocytes might be a promising MS therapeutic target.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":" ","pages":"90-95"},"PeriodicalIF":2.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141878682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Innate ImmunityPub Date : 2024-07-01Epub Date: 2024-08-01DOI: 10.1177/17534259241269687
Elias Jeradeh, Christian Frangie, Samer Bazzi, Jalil Daher
{"title":"The <i>in vitro</i> effect of myeloperoxidase oxidized LDL on THP-1 derived macrophages.","authors":"Elias Jeradeh, Christian Frangie, Samer Bazzi, Jalil Daher","doi":"10.1177/17534259241269687","DOIUrl":"10.1177/17534259241269687","url":null,"abstract":"<p><p>Cardiovascular diseases (CVDs) linked to atherosclerosis remains the leading cause of death worldwide. Atherosclerosis is primarily caused by the accumulation of oxidized forms of low density lipoprotein (LDL) in macrophages (MΦs) in the subendothelial layer of arteries leading to foam cell and fatty streak formation. Many studies suggest that LDL that is modified by myeloperoxidase (MPO) is a key player in the development of atherosclerosis. MΦs can adopt a variety of functional phenotypes that include mainly the proinflammatory M1 and the anti-inflammatory M2 MΦ phenotypes which are both implicated in the process of atherogenesis. In fact, MΦs that reside in atherosclerostic lesions were shown to express a variety of phenotypes ranging between the M1- and M2 MΦ types. Recently, we pointed out the involvement of MPO oxidized-LDL (Mox-LDL) in increasing inflammation in MΦs by reducing their secretion of IL-10. Since little is known about Mox-LDL-mediated pro-atherosclerostic responses in MΦs, our study aimed at analyzing the <i>in vitro</i> effects of Mox-LDL at this level through making use of the well-established model of human THP-1-derived Mφs. Our results demonstrate that Mox-LDL has no effect on apoptosis, reactive oxygen species (ROS) generation and cell death in our cell model; yet, interestingly, our results show that Mox-LDL is significantly engulfed at a higher rate in the different MΦ subtypes supporting its key role in foam cell formation during the progression of the disease as well as previous data that were generated using another primary MΦ cell model of atherosclerosis.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":" ","pages":"82-89"},"PeriodicalIF":2.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Myricetin reduces neutrophil extracellular trap release in a rat model of rheumatoid arthritis, which is associated with a decrease in disease severity.","authors":"Yiqin Shu, Rui Yang, Huijie Wen, Qiannan Dong, Zhiqi Chen, Yang Xiang, Hao Wu","doi":"10.1177/17534259241255439","DOIUrl":"10.1177/17534259241255439","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a chronic disease characterized by joint inflammation and severe disability. However, there is a lack of safe and effective drugs for treating RA. In our previous study, we discovered that myricetin (MC) and celecoxib have a synergistic effect in the treatment of RA. We conducted in vitro and in vivo experiments to further investigate the effects and mechanisms of action of MC. Our findings demonstrated that MC treatment effectively reduced the release of neutrophil extracellular traps (NETs) and alleviated the inflammatory response in RA. Mechanistic studies showed that MC prevents the entry of PADI4 and MPO into the cell nucleus, thereby protecting DNA from decondensation. In a rat arthritis model, MC improved histological changes in ankle joints and suppressed NET-related signaling factors. In conclusion, MC protects the ankle joints against arthritis by inhibiting MPO and PADI4, thereby reducing NET release. The pharmacological mechanism of MC in RA involves the inhibition of NET release.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":" ","pages":"66-78"},"PeriodicalIF":3.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11165658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}