International Journal of Inflammation最新文献

{"title":"Targeting P2X Receptors-Current Progress in Sepsis.","authors":"Lan Luo, Qian Zhao, Yunfen Tian, Meisha Sun, Mazhong Zhang, Bin Wang","doi":"10.1155/ijin/1083543","DOIUrl":"10.1155/ijin/1083543","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":14004,"journal":{"name":"International Journal of Inflammation","volume":"2025 ","pages":"1083543"},"PeriodicalIF":2.0,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12488317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Platelets and Their Role in Immunity: Formation, Activation and Activity, and Biologically Active Substances in Their Granules and Extracellular Vesicles.","authors":"Beata Tokarz-Deptuła, Łukasz Baraniecki, Joanna Palma, Michał Stosik, Anhelli Syrenicz, Roman Kołacz, Wiesław Deptuła","doi":"10.1155/ijin/8878764","DOIUrl":"10.1155/ijin/8878764","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":14004,"journal":{"name":"International Journal of Inflammation","volume":"2025 ","pages":"8878764"},"PeriodicalIF":2.0,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12479161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MLR Corresponds to the Functional Status of Monocytes in Chronic Lymphocytic Leukemia.","authors":"Wioleta Grzegorzewska, Michał Zarobkiewicz, Katarzyna Jastrzębska-Pawłowska, Natalia Lehman, Waldemar Tomczak, Magdalena Mizerska-Kowalska, Agnieszka Bojarska-Junak, Jacek Roliński","doi":"10.1155/ijin/4443773","DOIUrl":"10.1155/ijin/4443773","url":null,"abstract":"<p><p><b>Background:</b> 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. <b>Objectives:</b> 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. <b>Methods:</b> 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. <b>Results:</b> In our study, CLL patients had significantly lower values of MLR parameters compared to HVs (<i>p</i> < 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. <b>Conclusions:</b> 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.</p>","PeriodicalId":14004,"journal":{"name":"International Journal of Inflammation","volume":"2025 ","pages":"4443773"},"PeriodicalIF":2.0,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12356674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Netrin-1: Dual Roles in Neuroinflammation and Neurodegenerative Disease Dynamics.","authors":"Hadiseh Farahani, Ali Ganji, Ghasem Mosayebi, Mohsen Ebrahimi Monfared, Ali Ghazavi","doi":"10.1155/ijin/8670048","DOIUrl":"10.1155/ijin/8670048","url":null,"abstract":"<p><p>Netrin-1, a central axonal guidance molecule discovered for its role in neuronal development, is also essential in neurodegenerative diseases. Netrin-1 inhibits leukocyte migration and inflammation-related tissue damage outside the central nervous system. Therefore, it can be viewed as a potential biomarker for inflammatory activity in neurodegenerative diseases. Recent studies highlight the dual roles of Netrin-1 in neuroinflammation and neurodegenerative diseases. In the context of neurodegeneration, Netrin-1 demonstrates both protective and harmful effects. This review highlights recent advancements in research regarding the dual roles of Netrin-1 in neuroinflammation and neurodegeneration. We discuss its involvement in protecting the blood-brain barrier (BBB) and regulating immune cell migration and its effects on various neurodegenerative diseases. A greater understanding of the multifunctionality of Netrin-1 could potentially be employed in developing new treatment modalities.</p>","PeriodicalId":14004,"journal":{"name":"International Journal of Inflammation","volume":"2025 ","pages":"8670048"},"PeriodicalIF":2.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12321422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144784206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of Metabolic Syndrome on Immune Regulation (IL-17, IL-23, and FOXP3+), Psoriasis Severity, Flare Frequency, and Quality of Life in Psoriasis Patients: A Cross-Sectional Study.","authors":"Flora Ramona Sigit Prakoeswa, Faradiba Maharani, Saiful Hidayat, Winda Atika Sari, Triasari Oktavriana, Cita Rosita Sigit Prakoeswa, Menul Ayu Umborowati, Ratih Pramuningtyas, Rochmadina Suci Bestari, Riandini Aisyah, Erika Diana Risanti, Listiana Masyita Dewi, Ilham Hafizha Maulana Anam","doi":"10.1155/ijin/5855171","DOIUrl":"10.1155/ijin/5855171","url":null,"abstract":"<p><p><b>Introduction:</b> Psoriasis is a chronic inflammatory skin disease that exhibits a strong association with metabolic syndrome (MetS). The involvement of various proinflammatory cytokines in MetS is thought to play a critical role in the pathogenesis of psoriasis. This study aims to evaluate the impact of MetS on immunological markers (IL-17, IL-23, and FOXP3+ regulatory T cells), disease severity, and quality of life (QoL) among patients with psoriasis. <b>Methods:</b> This cross-sectional study involved 42 psoriasis patients, divided into two groups: 29 without MetS (Pso) and 13 with MetS (Pso-MetS). Clinical parameters such as blood pressure, fasting blood glucose, and triglyceride levels were measured. Immunological markers (IL-17, IL-23, and FOXP3+) were analyzed using ELISA. Psoriasis severity was assessed using the Psoriasis Area and Severity Index (PASI), and QoL was evaluated with the Dermatology Life Quality Index (DLQI). <b>Results:</b> The Pso-MetS group was significantly older than the Pso group (<i>p</i> value = 0.003). Higher systolic (<i>p</i> value < 0.001), fasting glucose (<i>p</i> value = 0.002), and triglycerides (<i>p</i> value < 0.001) were observed in the Pso-MetS group. Lower HDL observed in the Pso-MetS group (<i>p</i> value = 0.004). FOXP3+ expression was significantly lower in the Pso-MetS group (<i>p</i>=0.02), while waist circumference, diastolic blood pressure, IL-17, IL-23, PASI, and DLQI scores levels showed no significant differences. <b>Conclusions:</b> MetS is associated with immune dysregulation, evidenced by reduced FOXP3+ expression in psoriasis patients. Further studies are needed to explore the immunological link between psoriasis and MetS.</p>","PeriodicalId":14004,"journal":{"name":"International Journal of Inflammation","volume":"2025 ","pages":"5855171"},"PeriodicalIF":2.6,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Are Salivary and Plasma Levels of Toll-Like Receptors 2 and 4 Elevated in Subjects With Chronic Periodontitis?: A Systematic Review and Meta-Analysis.","authors":"Mario Alberto Alarcón-Sánchez, Ruth Rodríguez-Montaño, Sarah Monserrat Lomelí-Martínez, Cristina Hermila Martínez-Bugarin, Seyed Ali Mosaddad, Artak Heboyan","doi":"10.1155/ijin/7405066","DOIUrl":"https://doi.org/10.1155/ijin/7405066","url":null,"abstract":"<p><p>Toll-like receptors (TLR2 and TLR4) are crucial in the detection of pathogen-associated molecular patterns (PAMPs) during periodontitis, resulting in exacerbated production of proinflammatory cytokines and ultimately tissue damage and bone loss associated with this periodontal disease. This systematic review and meta-analysis aimed to systematically analyze and quantify the differences between TLR2 and TLR4 levels in the saliva and plasma of individuals with chronic periodontitis (CP) and systemically and periodontally healthy subjects (SPHS). The databases consulted were Scopus, Web of Science, and PubMed from 2011 to 2024 to locate cross-sectional studies that measured TLR2 and TLR4 levels. Studies selected were human research articles published in English, evaluating these biomarkers through ELISA. Data were extracted, and the quality of studies was appraised using the Joanna Briggs Institute (JBI) tool for observational studies. Meta-analyses were executed using STATA V.15 (StataCorp LP, College Station, Texas) employing fixed or random-effects models based on the degree of heterogeneity using I² statistics. Out of 404 articles found, four studies were included for both qualitative and quantitative synthesis. We found an increase in salivary TLR4 levels in subjects with CP compared with SPHS (SMD = 265.217 (95% confidence interval (CI) = 109.311-421.122); <i>p</i>=0.001). As well as an increase in plasma levels of TLR4 in subjects with CP compared with SPHS (SMD = 2.93 (95% CI = 1.57-4.29); <i>p</i>=0.001). TLR4 concentrations in saliva and plasma of subjects with CP were higher than those observed in the healthy population. However, further validation in larger prospective studies is needed before clinical implementation.</p>","PeriodicalId":14004,"journal":{"name":"International Journal of Inflammation","volume":"2025 ","pages":"7405066"},"PeriodicalIF":2.6,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12074830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144077992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein Interaction Analysis and Molecular Simulation of the Anti-Inflammatory Activities in <i>Melaleuca cajuputi</i> Extract Against COVID-19.","authors":"Agustyas Tjiptaningrum, Intanri Kurniati, Fadilah Fadilah, Tiwuk Susantiningsih, Aisyah Fitriannisa Prawiningrum, Wahyu Dian Utari, Linda Erlina","doi":"10.1155/ijin/5568294","DOIUrl":"10.1155/ijin/5568294","url":null,"abstract":"<p><p>Coronavirus disease-19 (COVID-19) is correlated to a severe condition caused by a cytokine storm during which numerous proinflammatory cytokines, including interleukin-6 (IL-6) are released. IL-6 is a critical driver in the COVID-19 inflammatory state, and the inhibition is considered a potential treatment approach to prevent serious complications. Meanwhile, <i>Melaleuca cajuputi</i> is a plant with antibacterial, antiviral, anti-inflammatory, and antioxidant activities. Therefore, this aimed to investigate the anti-inflammatory potential of <i>M. cajuputi</i> in silico. Extraction of leaves was conducted by using 96% ethanol, followed by fractionation to obtain active compounds. Subsequently, LC/MS and GC/MS analyses were performed to obtain active compound profiling. Protein-protein interaction (PPI), as well as molecular docking and dynamic analyses, were performed to examine interaction of active compounds of <i>M. cajuputi</i> with IL-6. The results showed that 30 protein nodes played a significant role in COVID-19 cytokine storm and eight active compounds had interactions with IL-6. Among the active compounds, pinostrobin chalcone had the best delta G interaction with IL-6. In conclusion, <i>M. cajuputi</i> has potential activity as an anti-inflammatory agent against COVID-19.</p>","PeriodicalId":14004,"journal":{"name":"International Journal of Inflammation","volume":"2024 ","pages":"5568294"},"PeriodicalIF":2.6,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11620808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extended Inflammation Parameters (EIP) as Markers of Inflammation in Systemic Sclerosis.","authors":"Anna Kowalska-Kępczyńska, Mateusz Mleczko, Kamila Komajda, Małgorzata Michalska-Jakubus, Dorota Krasowska, Maciej Korpysz","doi":"10.1155/2024/3786206","DOIUrl":"10.1155/2024/3786206","url":null,"abstract":"<p><strong>Background: </strong>Systemic sclerosis (SSc) is an autoimmune disease characterized by inflammation, progressive vasculopathy, and fibrosis of skin and internal organs. The aim of the study was to evaluate extended inflammatory parameters (EIP) in patients with SSc in comparison to the control group of healthy subjects.</p><p><strong>Methods: </strong>A total of 28 patients with SSc and 29 healthy controls (HCs) were included in the study. The following EIP parameters were analyzed: neutrophil reactive intensity (NEUT-RI), neutrophil granularity intensity (NEUT-GI), antibody-synthesizing lymphocytes (AS-LYMP), and reactive lymphocytes (RE-LYMP).</p><p><strong>Results: </strong>Patients with SSc showed significantly higher values of parameters determining neutrophil reactivity and neutrophil granularity when compared to HCs (respectively, 49.16 FI vs. 44.33 FI, <i>p</i> < 0.001, and 152.01 SI vs. 147.51 SI, <i>p</i> < 0.001). Moreover, patients with SSc had higher absolute numbers of RE-LYMP than HCs (0.69 × 10³/<i>µ</i>l vs. 0.04 × 10³/<i>µ</i>l, <i>p</i> < 0.001). Importantly, significant correlations between the RE-LYMP and either IL-6 (<i>R</i> = 0.447, <i>p</i> < 0.001) or ESR (<i>R</i> = 0.532, <i>p</i> < 0.001) were found among patients with SSc.</p><p><strong>Conclusions: </strong>Changes in NEUT-RI, NEUT-GI, and RE-LYMP levels positively correlate with inflammation in SSc and, thus, could potentially be used as an additional reliable inflammatory biomarker to assess inflammation in this disease.</p>","PeriodicalId":14004,"journal":{"name":"International Journal of Inflammation","volume":"2024 ","pages":"3786206"},"PeriodicalIF":2.6,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11449563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142374013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of Endotoxin-Induced Inflammation on the Activity of the Somatotropic Axis in Sheep.","authors":"Maciej Wójcik, Dorota Anna Zieba, Joanna Bochenek, Agata Krawczyńska, Marcin Barszcz, Alina Gajewska, Hanna Antushevich, Andrzej Przemysław Herman","doi":"10.1155/2024/1057299","DOIUrl":"10.1155/2024/1057299","url":null,"abstract":"<p><p>The hypothalamic-pituitary-somatotropic (HPS) axis controls many physiological and pathophysiological processes. The phenomenon of insensitivity to growth hormone resistance (GHres) was previously reported to be due to the development of inflammation. Therefore, the primary aim of the study was to determine the impact of inflammation caused by lipopolysaccharides (LPS) on the secretory activity of the HPS axis in sheep. The further goal was to determine the effect of inflammatory factors on individual components involved in intracellular signal transduction to GH via the GH receptor (GHR). The research was carried out on 24 seasonal sheep kept under a short-day photoperiod, randomly divided into two groups. Before the experiment, the sheep estrous cycles were synchronized. The results of the current study in a sheep model showed that inflammation impairs the activity of the somatotropic axis. On the one hand, LPS injection stimulated (<i>p</i> < 0.01) GH secretion, and on the other hand, it reduced the liver's sensitivity to this hormone by directly reducing (<i>p</i> < 0.01) GHR expression and activating the GHR inhibitory signal transduction mechanism. A symptom of such an inhibitory postreceptor signaling pathway may be due to an increase in SOCS3 expression (<i>p</i> < 0.01). The effect of various inhibition pathways is a significant reduction in the expression of the main transcription activator IGF1-STAT5B (<i>p</i> < 0.05). The action of GHres in the liver resulted in the inhibition of IGF1 secretion, which in the long term may have negative consequences for growth and development. Our study suggests that disruption of the GH cell signaling pathway may be one of the important elements of the pathophysiology of inflammation. It can suppress growth and hepatic metabolism to spare energy expenditure.</p>","PeriodicalId":14004,"journal":{"name":"International Journal of Inflammation","volume":"2024 ","pages":"1057299"},"PeriodicalIF":2.6,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11325012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of a New Immunosuppressive and Antimicrobial Peptide, DRS-DA2, Isolated from the Mexican Frog, <i>Pachymedusa dacnicolor</i>.","authors":"Claire Lacombe, Estefania Aleman-Navaro, Thierry Drujon, Veronica Martinez-Osorio, Emmanuelle Sachon, Erika Melchy-Pérez, Ludovic Carlier, Lorena Elizabeth Fajardo Brigido, Yannick Fleury, Christophe Piesse, Guadalupe Gutiérrez-Escobedo, Alejandro De Las Peñas, Irene Castaño, Florie Desriac, Jose Luis Beristain-Hernandez, Christophe Combadiere, Yvonne Rosenstein, Constance Auvynet","doi":"10.1155/2024/2205864","DOIUrl":"10.1155/2024/2205864","url":null,"abstract":"<p><p>Inflammatory and antimicrobial diseases constitute a major burden for society, and fighting them is a WHO strategic priority. Most of the treatments available to fight inflammatory diseases are anti-inflammatory drugs, such as corticosteroids or immunomodulators that lack cellular specificity and lead to numerous side effects. In addition to suppressing undesired inflammation and reducing disease progression, these drugs lessen the immune system protective functions. Furthermore, treating infectious diseases is more and more challenging due to the rise of microbial resistance to antimicrobial drugs. Thus, controlling the inflammatory process locally without compromising the ability to combat infections is an essential feature in the treatment of inflammatory diseases. We isolated three forms (DRS-DA2N, DRS-DA2NE, and DRS-DA2NEQ) of the same peptide, DRS-DA2, which belongs to the dermaseptin family, from the Mexican tree frog <i>Pachymedusa dacnicolor</i>. Interestingly, DRS-DA2N and DRS-DA2NEQ exhibit a dual activity by inducing the death of leukocytes as well as that of Gram-negative and Gram-positive bacteria, including multiresistant strains, without affecting other cells such as epithelial cells or erythrocytes. We showed that the death of both immune cells and bacteria is induced rapidly by DRS-DA2 and that the membrane is permeabilized, leading to the loss of membrane integrity. We also validated the capacity of DRS-DA2 to regulate the pool of inflammatory cells <i>in vivo</i> in a mouse model of noninfectious peritonitis. After the induction of peritonitis, a local injection of DRS-DA2N could decrease the number of inflammatory cells locally in the peritoneal cavity without inducing a systemic effect, as no changes in the number of inflammatory cells could be detected in blood or in the bone marrow. Collectively, these data suggest that this peptide could be a promising tool in the treatment of inflammatory diseases, such as inflammatory skin diseases, as it could reduce the number of inflammatory cells locally without suppressing the ability to combat infections.</p>","PeriodicalId":14004,"journal":{"name":"International Journal of Inflammation","volume":"2024 ","pages":"2205864"},"PeriodicalIF":2.0,"publicationDate":"2024-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10799709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139512406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}