Benjamin Sanchez, Sandra Ferraro, Audrey Josset-Lamaugarny, Aurélie Pagnon, Charlie K Hee, Lauren Nakab, Dominique Sigaudo-Roussel, Bérengère Fromy
{"title":"Skin Cell and Tissue Responses to Cross-Linked Hyaluronic Acid in Low-Grade Inflammatory Conditions.","authors":"Benjamin Sanchez, Sandra Ferraro, Audrey Josset-Lamaugarny, Aurélie Pagnon, Charlie K Hee, Lauren Nakab, Dominique Sigaudo-Roussel, Bérengère Fromy","doi":"10.1155/2023/3001080","DOIUrl":"https://doi.org/10.1155/2023/3001080","url":null,"abstract":"<p><p>Hyaluronic acid (HA), used in a variety of medical applications, is associated in rare instances to long-term adverse effects. Although the aetiology of these events is unknown, a number of hypotheses have been proposed, including low molecular weight of HA (LMW-HA) in the filler products. We hypothesized that cross-linked HA and its degradation products, in a low-grade inflammatory microenvironment, could impact immune responses that could affect cell behaviours in the dermis. Using two different cross-linking technologies VYC-15L and HYC-24L+, and their hyaluronidase-induced degradation products, we observed for nondegraded HA, VYC-15L and HYC-24L+, a moderate and transient increase in IL-1<i>β</i>, TNF-<i>α</i> in M1 macrophages under low-grade inflammatory conditions. Endothelial cells and fibroblasts were preconditioned using inflammatory medium produced by M1 macrophages. 24 h after LMW-HA fragments and HA stimulation, no cytokine was released in these preconditioned cells. To further characterize HA responses, we used a novel <i>in vivo</i> murine model exhibiting a systemic low-grade inflammatory phenotype. The intradermal injection of VYC-15L and its degradation products induced an inflammation and cell infiltration into the skin that was more pronounced than those by HYC-24L+. This acute cutaneous inflammation was likely due to mechanical effects due to filler injection and tissue integration rather than its biological effects on inflammation. VYC-15L and its degradation product potentiated microvascular response to acetylcholine in the presence of a low-grade inflammation. The different responses with 2D cell models and mouse model using the two tested cross-linking HA technologies showed the importance to use integrative complex model to better understand the effects of HA products according to inflammatory state.</p>","PeriodicalId":14004,"journal":{"name":"International Journal of Inflammation","volume":"2023 ","pages":"3001080"},"PeriodicalIF":2.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10474960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10208786","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":"Relationships between Inflammatory Biomarkers and Fatigue among Patients with Moderate and Severe COVID-19.","authors":"Besher A Gharaibeh, Jehad Rababah, Obieda Haneyah","doi":"10.1155/2023/7057458","DOIUrl":"https://doi.org/10.1155/2023/7057458","url":null,"abstract":"<p><strong>Background: </strong>Patients with moderate or severe COVID-19 infection suffer from varying levels of fatigue; however, there is a lack of understanding regarding the effect of inflammation on fatigue; and whether these relationships differ according to the severity of the infection.</p><p><strong>Aim: </strong>To assess the relationships between selected inflammatory biomarkers and fatigue levels among hospitalized Jordanian patients with moderate or severe COVID-19 infection.</p><p><strong>Methods: </strong>A quantitative cross-sectional design was used. A total of 352 participants were recruited for the study. Data regarding fatigue type and level were collected using the Chalder fatigue scale. Laboratory test results regarding several selected inflammatory biomarkers (e.g., ESR, CRP, IL-6, D-dimer, and others) were collected from patient records. The severity of the COVID-19 infection was determined using the criteria of the Ministry of Health in Jordan based on the results of O<sub>2</sub>% (oxygen saturation).</p><p><strong>Results: </strong>The mean scores of the total fatigue level significantly differed between the two levels of the severity of COVID-19 infection (moderate and severe levels) (<i>t</i> = -3.0, <i>p</i> < 0.05). Similar findings were observed with physiological fatigue (<i>t</i> = -3.50, <i>p</i> < 0.05), and no significant difference was observed in psychological fatigue. Out of the selected inflammatory markers, only neutrophil and lymphocyte count had a significant influence on total fatigue level.</p><p><strong>Conclusion: </strong>The level and type of fatigue was affected by the severity of the disease. However, the disease process itself represented by the levels of the inflammatory markers showed little influence on fatigue. The implications such as continuous screening of fatigue, and monitoring of the levels of the inflammatory markers are important to assist in diagnosing and managing COVID-19 patients. Furthermore, the relationship between the inflammatory process and fatigue is complex and requires further exploration.</p>","PeriodicalId":14004,"journal":{"name":"International Journal of Inflammation","volume":"2023 ","pages":"7057458"},"PeriodicalIF":2.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10164871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9446586","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}
T. Ollewagen, Gareth Tarr, K. Myburgh, H. Reuter, Carine Smith
{"title":"Therapeutic Benefit in Rheumatoid Cachexia Illustrated Using a Novel Primary Human Triple Cell Coculture Model","authors":"T. Ollewagen, Gareth Tarr, K. Myburgh, H. Reuter, Carine Smith","doi":"10.1155/2022/1524913","DOIUrl":"https://doi.org/10.1155/2022/1524913","url":null,"abstract":"Background The loss of muscle mass in rheumatoid arthritis (RA), termed rheumatoid cachexia, is predicted to result from the complex interactions between different cell types involved in the maintenance of skeletal muscle mass, namely, myoblasts, fibroblasts, and macrophages. The complexity within the muscle is further highlighted by the incidence of nonresponsiveness to current RA treatment strategies. Method This study aimed at determining differences in the cellular responses in a novel human primary cell triple coculture model exposed to serum collected from nonarthritic controls (NC), RA treatment naïve (RATN), and RA treatment-nonresponding (RATNR) patients. Bone morphogenetic protein-7 (BMP-7) was investigated as a treatment option. Results Plasma analysis indicated that samples were indeed representative of healthy and RA patients—notably, the RATNR patients additionally exhibited dysregulated IL-6/IL-10 correlations. Coculture exposure to serum from RATNR patients demonstrated increased cellular growth (p < 0.001), while both hepatocyte growth factor (p < 0.01) and follistatin (p < 0.001) were reduced when compared to NC. Furthermore, decreased concentration of markers of extracellular matrix formation, transforming growth factor-β (TGF-β; p < 0.05) and fibronectin (p < 0.001), but increased collagen IV (p < 0.01) was observed following RATNR serum exposure. Under healthy conditions, BMP-7 exhibited potentially beneficial results in reducing fibrosis-generating TGF-β (p < 0.05) and fibronectin (p < 0.05). BMP-7 further exhibited protective potential in the RA groups through reversing the aberrant tendencies observed especially in the RATNR serum-exposed group. Conclusion Exposure of the triple coculture to RATN and RATNR serum resulted in dysregulated myoblast proliferation and growth, and ECM impairment, which was reversed by BMP-7 treatment.","PeriodicalId":14004,"journal":{"name":"International Journal of Inflammation","volume":"54 18","pages":""},"PeriodicalIF":2.0,"publicationDate":"2022-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72369520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
F. Fesahat, Efat Norouzi, S. Seifati, Saeideh Hamidian, A. Hosseini, F. Zare
{"title":"Impact of Vitamin C on Gene Expression Profile of Inflammatory and Anti-Inflammatory Cytokines in the Male Partners of Couples with Recurrent Pregnancy Loss","authors":"F. Fesahat, Efat Norouzi, S. Seifati, Saeideh Hamidian, A. Hosseini, F. Zare","doi":"10.1155/2022/1222533","DOIUrl":"https://doi.org/10.1155/2022/1222533","url":null,"abstract":"Immune system disorders and increased inflammation in the male reproductive system can lead to fetal risk in the early stages of development and implantation. Antioxidants such as vitamin C can play a protective role against sperm inflammatory reactions. This study aimed to evaluate the effect of vitamin C on the expression of inflammatory and anti-inflammatory cytokine genes in the male partners of couples with recurrent pregnancy loss. In this randomized clinical trial, twenty male partners of couples with RPL were examined for sperm parameters and expression profile of some inflammatory and anti-inflammatory cytokine genes before and after treatment with vitamin C. There was a statistically significant higher rate of normal morphology and sperm concentration in each patient before and after treatment with vitamin C (p ≤ 0.05). The mRNA levels of interleukin 6 and tumor necrosis factor-alpha were significantly decreased in the sperm of patients after treatment with vitamin C compared to before treatment. In contrast, the gene expression levels of interleukin 4 and transforming growth factor-beta showed a significant increase in the sperm of patients after treatment with vitamin C. Oral daily administration of vitamin C may be effective in the fertility potential of male partners of couples with RPL not only through the improvement of the sperm parameters but also by modulating the expression profile of inflammatory and anti-inflammatory genes. Further studies on protein levels are needed to clarify the role of TNF-⍺ and IFN-γ as a prognostic value in evaluating the recurrent abortion risk in infertile male partners. This trial is registered with IRCT20180312039059N1.","PeriodicalId":14004,"journal":{"name":"International Journal of Inflammation","volume":"31 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2022-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81873765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mortality Associated with Recurrent Extreme Hyperferritinemia in Critically Ill Adolescents","authors":"J. Baird","doi":"10.1155/2022/6207417","DOIUrl":"https://doi.org/10.1155/2022/6207417","url":null,"abstract":"Introduction Recurrent extreme hyperferritinemia (ferritin >10,000 ng/mL) was noted in 4 critically ill adolescents prior to death, though this association has not previously been described. Methods A retrospective review of the medical records of 4 critically ill adolescents with recurrent extreme hyperferritinemia and systemic inflammation was performed to identify additional common epidemiologic factors. Results Systemic inflammation was characterized as cytokine storm syndrome in 2 patients and hemophagocytic lymphohistiocytosis in 2 patients. Episodes of extreme hyperferritinemia were noted on at least 2 different dates in all patients; these episodes (n = 10) were separated by an interval of 2 weeks to several months and were usually (in 8 of 10 episodes) associated with the onset or worsening of multiple organ dysfunction syndrome. Death occurred within 2 weeks of the onset of an episode of recurrent extreme hyperferritinemia. Lymphocytopenia and cachexia were noted in all patients. Conclusions Recurrent extreme hyperferritinemia—often with multiple organ dysfunction syndrome—was noted in 4 adolescents with systemic inflammation who did not survive their critical illness. Recurrent extreme hyperferritinemia may be a novel biomarker of increased mortality in patients with the syndrome of persistent inflammation, immunosuppression, and catabolism.","PeriodicalId":14004,"journal":{"name":"International Journal of Inflammation","volume":"29 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2022-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78143601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L. Castoldi, G. Romagnoli, M. de Assis Golim, O. Ribeiro, Olga Célia Martinez Ibañez, D. Maria, Andréa Vanessa Pinto Domeneghini, M. C. Gameiro, P. R. Martins, M. Mischan, R. Kaneno
{"title":"Cytotoxic Activity and Lymphocyte Subtypes in Mice Selected for Maximal and Minimal Inflammatory Response after Transplantation of B16F10 and S91 Melanoma Cells","authors":"L. Castoldi, G. Romagnoli, M. de Assis Golim, O. Ribeiro, Olga Célia Martinez Ibañez, D. Maria, Andréa Vanessa Pinto Domeneghini, M. C. Gameiro, P. R. Martins, M. Mischan, R. Kaneno","doi":"10.1155/2022/3298542","DOIUrl":"https://doi.org/10.1155/2022/3298542","url":null,"abstract":"AIRmax and AIRmin mice strains were selected according to the intensity of their acute inflammatory responsiveness. Previous studies have shown that AIR mice differ in their resistance to chemically induced skin tumors and in the development of melanoma metastases, in addition to differences in neutrophil and NK cells activity. In the present work, we aimed to evaluate whether the difference of susceptibility to murine melanoma is associated with NK cytotoxic activity against Yac.1 cells and lymphocyte subsets. Mice were subcutaneously inoculated with B16F10 or S91 melanoma cells. After 7, 14, or 30 days, the animals were euthanized to analyze the number of lymphocyte subsets, cytotoxic activity, and number of cytokine-producing spleen cells. AIRmax mice presented a higher number of CD4+/CD25+ cells than that of AIRmin mice following inoculation of B16F10 cells, whereas inoculation of S91 cells reduced CD4+/CD25+ and increased TCD8+ cell subsets in the AIRmax mice. AIRmax mice had a higher number of interleukin (IL)-10- and IL-12-producing cells and a lower number of interferon-γ–producing cells than those of AIRmin mice at 30 days. The cytotoxic activity of nonadherent spleen cells was similar in both the AIR strains. These results suggest that melanoma cells can induce different responses in AIR mice, possibly owing to alterations in regulatory mechanisms, such as the action of CD4+/CD25+ regulatory T cells and IL-10, in AIRmax mice.","PeriodicalId":14004,"journal":{"name":"International Journal of Inflammation","volume":"26 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2022-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78319643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Habas, Srinivasa Reddy Natala, Jon K. Bowden-Verhoek, E. Stocking, D. Price, W. Wrasidlo, D. Bonhaus, Martin B. Gill
{"title":"NPT1220-312, a TLR2/TLR9 Small Molecule Antagonist, Inhibits Pro-Inflammatory Signaling, Cytokine Release, and NLRP3 Inflammasome Activation","authors":"A. Habas, Srinivasa Reddy Natala, Jon K. Bowden-Verhoek, E. Stocking, D. Price, W. Wrasidlo, D. Bonhaus, Martin B. Gill","doi":"10.1155/2022/2337363","DOIUrl":"https://doi.org/10.1155/2022/2337363","url":null,"abstract":"Toll-like receptors (TLRs) play a critical role in innate immune system responses to damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs). A growing body of evidence suggests that excessive TLR-mediated innate immune system activation can lead to neuronal damage and precipitate or perpetuate neurodegenerative diseases. Among TLR subtypes, both TLR2 and TLR9 have been implicated in neurodegenerative disorders with increased expression of these receptors in the central nervous system being associated with pro-inflammatory signaling and increased burdens of pathologic aggregated proteins. In the current study, we characterized the actions of a combined TLR2/TLR9 antagonist, NPT1220-312, on pro-inflammatory signaling and cytokine release in monocyte/macrophage-derived heterologous cells, human microglia, and murine and human whole blood. NPT1220-312 potently blocked TLR2- and TLR9-mediated release of inflammatory cytokines in monocyte/macrophage cells and in human microglia. NPT1220-312 also blocked TLR2-mediated activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome including IL-1β, IL-18, and apoptosis-associated speck-like protein containing a CARD (ASC) release to the culture medium of human differentiated macrophages. The ability of NPT1220-312 to inhibit TLR2 mediated pro-inflammatory release of chemokines and cytokines in situ was demonstrated using murine and human whole blood. Together, these findings suggest that blockade of TLR2 and TLR9 may reduce inappropriate production of pro-inflammatory cytokines and chemokines from peripheral and central immune cells and thus potentially provide therapeutic benefit in neuroinflammatory/neurodegenerative disorders.","PeriodicalId":14004,"journal":{"name":"International Journal of Inflammation","volume":"54 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2022-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82104267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"OMICS Approaches Evaluating Keloid and Hypertrophic Scars.","authors":"Nazihah Bakhtyar, Saeid Amini-Nik, Marc G Jeschke","doi":"10.1155/2022/1490492","DOIUrl":"https://doi.org/10.1155/2022/1490492","url":null,"abstract":"<p><p>Abnormal scar formation during wound healing can result in keloid and hypertrophic scars, which is a major global health challenge. Such abnormal scars can cause significant physiological pain and psychological distress and become a financial burden. Due to the biological complexity of scar formation, the pathogenesis of such scars and how to prevent them from forming remains elusive. In this review paper, we delve into the world of \"omics\" approaches to study abnormal scars and provide examples of genomics, transcriptomics, proteomics, epigenomics, and metabolomics. The benefits of \"omics\" approaches are that they allow for high-throughput studies and the analysis of 100s to 1000s of genes and proteins with the accumulation of large quantities of data. Currently in the field, there is a lack of \"omics\" review articles describing pathological scars. In this review, we summarize genome-wide linkage analysis, genome-wide association studies, and microarray data to name a few omics technologies. Such data can provide novel insights into different molecular pathways and identify novel factors which may not be captured through small-scale laboratory techniques.</p>","PeriodicalId":14004,"journal":{"name":"International Journal of Inflammation","volume":"2022 ","pages":"1490492"},"PeriodicalIF":2.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9722497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9462234","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":"Alterations in Immune-Related Defensin Alpha 4 (<i>DEFA4</i>) Gene Expression in Health and Disease.","authors":"Fatemah Basingab, Abeer Alsaiary, Shahad Almontashri, Aisha Alrofaidi, Mona Alharbi, Sheren Azhari, Khloud Algothmi, Safiah Alhazmi","doi":"10.1155/2022/9099136","DOIUrl":"https://doi.org/10.1155/2022/9099136","url":null,"abstract":"<p><p>Defensin Alpha 4 (DEFA4) is the fourth member of the Alpha Defensins family known as a part of antimicrobial peptides in the innate immune system. DEFA4 has a strong preference to kill Gram-negative bacteria more than Gram-positive bacteria. In addition, DEFA4 exhibits antiviral activity against human immunodeficiency virus type 1 (HIV-1) <i>in vitro</i>. Moreover, DEFA4 can act as an inhibitor of corticosterone production (Corticostatin). On the other hand, alternations in <i>DEFA4</i> gene expression have been reported in different disorders such as diseases related to inflammation and immunity dysfunction, brain-related disorders, and various cancers. The up-regulation of <i>DEFA4</i> appears to be involved in the malignant transformation or aggressive form of cancer. Interestingly, the modified version of DEFA4 fragment (1-11) was potent and efficient against antibiotic-resistant bacteria. This review provides a general background abSaudi Arabia out <i>DEFA4</i> and sheds light on changes in <i>DEFA4</i> gene expression in different diseases. The paper also discusses other aspects related to DEFA4 as an antimicrobial and antiviral agent. The research was conducted based on available articles obtained from databases starting from 1988 to the present.</p>","PeriodicalId":14004,"journal":{"name":"International Journal of Inflammation","volume":"2022 ","pages":"9099136"},"PeriodicalIF":2.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9167129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10619834","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 Restoring Effect of Human Umbilical Cord-Derived Mesenchymal Cell-Conditioned Medium (hMSC-CM) against Carbon Tetrachloride-Induced Pulmonary Fibrosis in Male Wistar Rats.","authors":"Maryam Khajvand-Abedini, Mahdi Bahmani, Nasrin Ziamajidi, Alireza Nourian, Parisa Habibi, Shirin Heidarisasan, Roghayeh Abbasalipourkabir","doi":"10.1155/2022/7179766","DOIUrl":"https://doi.org/10.1155/2022/7179766","url":null,"abstract":"<p><strong>Objective: </strong>Pulmonary toxicity induced by CCl<sub>4</sub>, a model of idiopathic pulmonary fibrosis (IPF), leads to tissue remodeling and inflammation. Human umbilical cord mesenchymal cell-conditioned medium (hMSC-CM) is a potent anti-inflammatory, antioxidative, and antifibrotic agent.</p><p><strong>Methods: </strong>Forty male Wistar rats were assigned to the control (C), olive oil control (C.O) (hMSC-CM), control (C.Ms), fibrosis (fb), and fibrosis with hMSC-CM (f.Ms) treatment groups. The groups C, C.O, and C.Ms received PBS (200 <i>µ</i>l), olive oil (1 ml/kg), and hMSC-CM (100 <i>μ</i>g protein/kg), respectively. The fibrosis group was administered with only CCl4 (1 ml/kg). The last group, f.Ms was treated with CCl<sub>4</sub> (1 ml/kg) and 100 <i>μ</i>g protein/kg IV hMSC-CM. While the treatment with olive oil and CCl<sub>4</sub> was performed for 2 days/week from the first week for 12 weeks, the treatment with PBS and hMSC-CM was carried out 2 days/week from week 4<sup>th</sup> to week 12<sup>th</sup>. The effect of the UC-MSC culture medium treatment on the lung was evaluated by assessing lysyl oxidase (LOX), tumor necrosis factor-alpha (TNF-<i>α</i>), and transforming growth factor-<i>β</i>1 (TGF-<i>β</i>1) genes, and proteins expression by real-time RCR and western blotting, respectively.</p><p><strong>Results: </strong>Lysyl oxidase (LOX), tumor necrosis factor-alpha (TNF-<i>α</i>), transforming growth factor-b1 (TGF-<i>β</i>1), malondialdehyde (MDA), and oxidative stress levels were markedly higher in the fibrosis group than in the control groups (<i>p</i> ≤ 0.001). Additionally, glutathione (GSH) in the fibrosis group was markedly lower than those in the control groups (<i>p</i> ≤ 0.001). Fibrosis in the UC-MSC treatment group had milder histopathological injuries than in the fibrosis group.</p><p><strong>Conclusion: </strong>hMSC-MSC as a strong anti-inflammatory, antioxidative, and antifibrotic decreases the level of oxidative stress, proinflammatory cytokines, and MDA causing a restoring effect against CCl<sub>4</sub>-induced pulmonary fibrosis.</p>","PeriodicalId":14004,"journal":{"name":"International Journal of Inflammation","volume":"2022 ","pages":"7179766"},"PeriodicalIF":2.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9800074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10466857","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}