Displaying publications 1 - 20 of 141 in total

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  1. Fulltext Modulation of interleukin-18 release produced positive outcomes on parasitaemia development and cytokines production during malaria in mice
    Basir R, Hasballah K, Jabbarzare M, Gam LH, Abdul Majid AM, Yam MF, et al.
    Trop Biomed, 2012 Sep;29(3):405-21.
    PMID: 23018504 MyJurnal
    The involvement of interleukin-18 (IL-18) and the effects of modulating its release on the course of malaria infection were investigated using Plasmodium berghei ANKA infection in ICR mice as a model. Results demonstrated that plasma IL-18 concentrations in malarial mice were significantly elevated and positively correlated with the percentage parasitaemia development. Significant expressions of IL-18 were also observed in the brain, spleen and liver tissues. Slower development of parasitaemia was observed significantly upon inhibition and neutralization of IL-18, whereas faster development of parasitaemia was recorded when the circulating levels of IL-18 were further augmented during the infection. Inhibition and neutralization of IL-18 production also resulted in a significant decrease of plasma concentrations of pro-inflammatory cytokines (TNFα, IFNγ, IL-1α and IL-6), whereas the anti-inflammatory cytokine, IL-10, was significantly increased. Augmenting the release of IL- 18 during the infection on the other hand resulted in the opposite. Early mortality in malarial mice was also observed when the circulating levels of IL-18 were further augmented. Results proved the important role of IL-18 in immune response against malaria and suggest that IL-8 is pro-inflammatory in nature and may involve in mediating the severity of the infection through a pathway of elevating the pro-inflammatory cytokine and limiting the release of anti-inflammatory cytokine.
    Matched MeSH terms: Cytokines/metabolism*
  2. A geranyl acetophenone targeting cysteinyl leukotriene synthesis prevents allergic airway inflammation in ovalbumin-sensitized mice
    Ismail N, Jambari NN, Zareen S, Akhtar MN, Shaari K, Zamri-Saad M, et al.
    Toxicol Appl Pharmacol, 2012 Mar 1;259(2):257-62.
    PMID: 22266348 DOI: 10.1016/j.taap.2012.01.003
    Asthma is associated with increased pulmonary inflammation and airway hyperresponsiveness. The current use of corticosteroids in the management of asthma has recently raised issues regarding safety and lack of responsiveness in 5-10% of asthmatic individuals. The aim of the present study was to investigate the therapeutic effect of a non-steroidal small molecule that has cysteinyl leukotriene (cysLT) inhibitory activity, upon attenuation of allergic lung inflammation in an acute murine model. Mice were sensitized with ovalbumin (OVA) and treated with several intraperitoneal doses (100, 20, 2 and 0.2mg/kg) of 2,4,6,-trihydroxy-3-geranylacetophenone (tHGA). Bronchoalveolar lavage was performed, blood and lung samples were obtained and respiratory function was measured. OVA sensitization increased pulmonary inflammation and pulmonary allergic inflammation was significantly reduced at doses of 100, 20 and 2mg/kg with no effect at the lowest dose of 0.2mg/kg. The beneficial effects in the lung were associated with reduced eosinophilic infiltration and reduced secretion of Th2 cytokines and cysLTs. Peripheral blood reduction of total IgE was also a prominent feature. Treatment with tHGA significantly attenuated altered airway hyperresponsiveness as measured by the enhanced pause (Penh) response to incremental doses of methacholine. These data demonstrate that tHGA, a synthetic non-steroidal small molecule, can prevent acute allergic inflammation. This proof of concept opens further avenues of research and development of tHGA as an additional option to the current armamentarium of anti-asthma therapeutics.
    Matched MeSH terms: Cytokines/metabolism
  3. Fulltext Impact of ellagic acid in bone formation after tooth extraction: an experimental study on diabetic rats
    Al-Obaidi MM, Al-Bayaty FH, Al Batran R, Hussaini J, Khor GH
    ScientificWorldJournal, 2014;2014:908098.
    PMID: 25485304 DOI: 10.1155/2014/908098
    To estimate the impact of ellagic acid (EA) towards healing tooth socket in diabetic animals, after tooth extraction.
    Matched MeSH terms: Cytokines/metabolism
  4. Fulltext Cytokines in infection
    Pang T
    Med J Malaysia, 1993 Mar;48(1):9-11.
    PMID: 8341179
    Cytokines are central to the development of effective immunity against microbial pathogens and their beneficial effects in the control of a variety of infections of man and animals are well-documented. However, it appears that cytokines may also have detrimental effects in infections by actually enhancing microbial growth. These observations emphasise the fact that many successful pathogens possess mechanisms enabling them to evade the immune response and that caution needs to be exercised in using cytokines as therapeutic agents to control infections in various human diseases.
    Matched MeSH terms: Cytokines/metabolism
  5. Fulltext Molecular responses during chemotherapy in acute myeloid leukemias in predicting poor-response to standard chemotherapy
    Maha A, Cheong SK, Leong CF, Seow HF
    Malays J Pathol, 2009 Dec;31(2):81-91.
    PMID: 20514850 MyJurnal
    Signal transduction pathways are constitutively expressed in leukaemic cells resulting in aberrant survival of the cells. It is postulated that in cells of chemo-sensitive patients, chemotherapy induces apoptotic signals leading to cell death while survival signals are maintained in cells of chemo-resistant patients. There is very little information currently, on the expression of these mediators in patients immediately after chemotherapy initiation. We examined the expression pattern of proinflammatory cytokines, signaling molecules of the PI3K and MAPK pathways molecules and death receptor, DR5 on paired samples at diagnosis and during chemotherapy in acute myeloid leukaemia patients treated with cytosine arabinoside and daunorubicin. The results were correlated with remission status one month after chemotherapy. We found that in chemo-sensitive patients, chemotherapy significantly increased the percentage of cases expressing TNF-alpha (p = 0.025, n = 9) and IL-6 (p = 0.002, n = 11) compared to chemo-resistant cases. We also observed an increased percentage of chemo-sensitive cases expressing DR5 and phosphorylated p38, and Jnk. Thus, expression of TNF-alpha, IL-6, DR5, phospho-p38 and phospho-Jnk may regulate cell death in chemo-sensitive cases. In contrast, a significantly higher percentage of chemo-resistant cases expressed phospho-Bad (p = 0.027, n = 9). IL-beta and IL-18 were also found to be higher in chemo-resistant cases at diagnosis and during chemotherapy. Thus, expression of various cellular molecules in leukaemic blasts during chemotherapy may be useful in predicting treatment outcome. These cellular molecules may also be potential targets for alternative therapy.
    Matched MeSH terms: Cytokines/metabolism
  6. Molecular factors in human implantation: adhesion molecules, proteases and cytokines
    Lim KJ
    Malays J Pathol, 2003 Jun;25(1):1-13.
    PMID: 16196373
    Successful human reproduction remains an enigma, but this is slowly changing in the current era of expanding scientific knowledge. The discovery of various molecular factors such as adhesion molecules, proteases and cytokines have in recent years been at the forefront of medical research. The growing importance of immunology in particular has led to novel new immuno-modulatory therapies and increasing research into this new aspect of reproductive immunology may well prove to be the most important breakthrough in understanding the fundamentals of human reproduction. Implantation represents the first step in the complex interactions and processes involved in foetal-maternal interaction, which continues throughout pregnancy gestation and culminates in the birth of an infant. It is therefore vital that we understand the myriad processes controlling implantation in order to build a firm foundation for exploring reproductive immunology research in the new millennium. This review brings together and presents an overview of the potential roles of currently known molecular factors such as adhesion molecules, proteases, cytokines and its interaction with the maternal immune response, incorporating the findings of previous published research performed by the author on cytokines and reproductive immunology.
    Matched MeSH terms: Cytokines/metabolism*
  7. Cytokine Induction in Nipah Virus-Infected Primary Human and Porcine Bronchial Epithelial Cells
    Elvert M, Sauerhering L, Maisner A
    J Infect Dis, 2020 05 11;221(Suppl 4):S395-S400.
    PMID: 31665348 DOI: 10.1093/infdis/jiz455
    During the Nipah virus (NiV) outbreak in Malaysia, pigs and humans were infected. While pigs generally developed severe respiratory disease due to effective virus replication and associated inflammation processes in porcine airways, respiratory symptoms in humans were rare and less severe. To elucidate the reasons for the species-specific differences in NiV airway infections, we compared the cytokine responses as a first reaction to NiV in primary porcine and human bronchial epithelial cells (PBEpC and HBEpC, respectively). In both cell types, NiV infection resulted in the expression of type III interferons (IFN-λ). Upon infection with similar virus doses, viral RNA load and IFN expression were substantially higher in HBEpC. Even if PBEpC expressed the same viral RNA amounts as NiV-infected HBEpC, the porcine cells showed reduced IFN- and IFN-dependent antiviral gene expression. Despite this inherently limited IFN response, the expression of proinflammatory cytokines (IL-6, IL-8) in NiV-infected PBEpC was not decreased. The downregulation of antiviral activity in the presence of a functional proinflammatory cytokine response might be one of the species-specific factors contributing to efficient virus replication and acute inflammation in the lungs of pigs infected with the Malaysian NiV strain.
    Matched MeSH terms: Cytokines/metabolism*
  8. Neuroinflammation pathways: a general review
    Shabab T, Khanabdali R, Moghadamtousi SZ, Kadir HA, Mohan G
    Int J Neurosci, 2017 Jul;127(7):624-633.
    PMID: 27412492 DOI: 10.1080/00207454.2016.1212854
    Activated microglial cells play an important role in immune and inflammatory responses in central nervous system and neurodegenerative diseases. Many pro-apoptotic pathways are mediated by signaling molecules that are produced during neuroinflammation. In glial cells, NF-κB, a transcription factor, initiates and regulates the expression of several inflammatory processes during inflammation which are attributed to the pathology of the several neurodegenerative diseases. In this review, we discuss the most important neuroinflammatory mediators with their pathways. Attenuating cytokines production and controlling microglial inflammatory response, which are the result of understanding neuroinflammation pathways, are considered therapeutic strategies for treating neurodegenerative diseases with an inflammatory component.
    Matched MeSH terms: Cytokines/metabolism*
  9. Fulltext A cell-based screening system for anti-influenza A virus agents
    Wong WY, Loh SW, Ng WL, Tan MC, Yeo KS, Looi CY, et al.
    Sci Rep, 2015;5:8672.
    PMID: 25728279 DOI: 10.1038/srep08672
    Emerging of drug resistant influenza A virus (IAV) has been a big challenge for anti-IAV therapy. In this study, we describe a relatively easy and safe cell-based screening system for anti-IAV replication inhibitors using a non-replicative strain of IAV. A nickel (II) complex of polyhydroxybenzaldehyde N4-thiosemicarbazone (NiPT5) was recently found to exhibit anti-inflammatory activity in vivo and in vitro. NiPT5 impedes the signaling cascades that lead to the activation of NF-κB in response to different stimuli, such as LPS and TNFα. Using our cell-based screening system, we report that pretreating cells with NiPT5 protects cells from influenza A virus (IAV) and vesicular stomatitis virus (VSV) infection. Furthermore, NiPT5 inhibits replication of IAV by inhibiting transcription and translation of vRNAs of IAV. Additionally, NiPT5 reduces IAV-induced type I interferon response and cytokines production. Moreover, NiPT5 prevents activation of NF-κB, and IRF3 in response to IAV infection. These results demonstrate that NiPT5 is a potent antiviral agent that inhibits the early phase of IAV replication.
    Matched MeSH terms: Cytokines/metabolism
  10. Fulltext Early clearance of Chikungunya virus in children is associated with a strong innate immune response
    Simarmata D, Ng DC, Kam YW, Lee B, Sum MS, Her Z, et al.
    Sci Rep, 2016 05 16;6:26097.
    PMID: 27180811 DOI: 10.1038/srep26097
    Chikungunya fever (CHIKF) is a global infectious disease which can affect a wide range of age groups. The pathological and immunological response upon Chikungunya virus (CHIKV) infection have been reported over the last few years. However, the clinical profile and immune response upon CHIKV infection in children remain largely unknown. In this study, we analyzed the clinical and immunological response, focusing on the cytokine/chemokine profile in a CHIKV-infected pediatric cohort from Sarawak, Malaysia. Unique immune mediators triggered upon CHIKV infection were identified through meta-analysis of the immune signatures between this pediatric group and cohorts from previous outbreaks. The data generated from this study revealed that a broad spectrum of cytokines/chemokines is up-regulated in a sub-group of virus-infected children stratified according to their viremic status during hospitalization. Furthermore, different immune mediator profiles (the levels of pro-inflammatory cytokines, chemokines and growth and other factors) were observed between children and adults. This study gives an important insight to understand the immune response of CHIKV infection in children and would aid in the development of better prognostics and clinical management for children.
    Matched MeSH terms: Cytokines/metabolism
  11. Fulltext Transcriptome analysis of chicken intraepithelial lymphocyte natural killer cells infected with very virulent infectious bursal disease virus
    Boo SY, Tan SW, Alitheen NB, Ho CL, Omar AR, Yeap SK
    Sci Rep, 2020 10 27;10(1):18348.
    PMID: 33110122 DOI: 10.1038/s41598-020-75340-x
    The infectious bursal disease (IBD) is an acute immunosuppressive viral disease that significantly affects the economics of the poultry industry. The IBD virus (IBDV) was known to infect B lymphocytes and activate macrophage and T lymphocytes, but there are limited studies on the impact of IBDV infection on chicken intraepithelial lymphocyte natural killer (IEL-NK) cells. This study employed an mRNA sequencing approach to investigate the early regulation of gene expression patterns in chicken IEL-NK cells after infection with very virulent IBDV strain UPM0081. A total of 12,141 genes were expressed in uninfected chicken IEL-NK cells, and most of the genes with high expression were involved in the metabolic pathway, whereas most of the low expressed genes were involved in the cytokine-cytokine receptor pathway. A total of 1,266 genes were differentially expressed (DE) at 3 day-post-infection (dpi), and these DE genes were involved in inflammation, antiviral response and interferon stimulation. The innate immune response was activated as several genes involved in inflammation, antiviral response and recruitment of NK cells to the infected area were up-regulated. This is the first study to examine the whole transcriptome profile of chicken NK cells towards IBDV infection and provides better insight into the early immune response of chicken NK cells.
    Matched MeSH terms: Cytokines/metabolism
  12. Poorly controlled type 1 diabetes mellitus seriously impairs female reproduction via immune and metabolic disorders
    Zhang S, Liu Q, Yang C, Li X, Chen Y, Wu J, et al.
    Reprod Biomed Online, 2024 Apr;48(4):103727.
    PMID: 38402677 DOI: 10.1016/j.rbmo.2023.103727
    RESEARCH QUESTION: Does type 1 diabetes mellitus (T1DM) affect reproductive health of female patients? What is the potential mechanism of reproductive dysfunction in female patients caused by T1DM?

    DESIGN: Preliminary assessment of serum levels of female hormones in women with or without T1DM. Then histological and immunological examinations were carried out on the pancreas, ovaries and uteri at different stages in non-obese diabetic (NOD) and Institute of Cancer Research (ICR) mice, as well as assessment of their fertility. A protein array was carried out to detect the changes in serum inflammatory cytokines. Furthermore, RNA-sequencing was used to identify the key abnormal genes/pathways in ovarian and uterine tissues of female NOD mice, which were further verified at the protein level.

    RESULTS: Testosterone levels were significantly increased (P = 0.0036) in female mice with T1DM. Increasing age in female NOD mice was accompanied by obvious lymphocyte infiltration in the pancreatic islets. Moreover, the levels of serum inflammatory factors in NOD mice were sharply increased with increasing age. The fertility of female NOD mice declined markedly, and most were capable of conceiving only once. Furthermore, ovarian and uterine morphology and function were severely impaired in NOD female mice. Additionally, ovarian and uterine tissues revealed that the differentially expressed genes were primarily enriched in metabolism, cytokine-receptor interactions and chemokine signalling pathways.

    CONCLUSION: T1DM exerts a substantial impairment on female reproductive health, leading to diminished fertility, potentially associated with immune disorders and alterations in energy metabolism.

    Matched MeSH terms: Cytokines/metabolism
  13. Influence of postbiotic RG14 and inulin combination on cecal microbiota, organic acid concentration, and cytokine expression in broiler chickens
    Kareem KY, Loh TC, Foo HL, Asmara SA, Akit H
    Poult Sci, 2017 Apr 01;96(4):966-975.
    PMID: 28339522 DOI: 10.3382/ps/pew362
    This study examined the effects of different combinations of inulin and postbiotics RG14 on growth performance, cecal microbiota, volatile fatty acids (VFA), and ileal cytokine expression in broiler chickens. Two-hundred-and sixteen, one-day-old chicks were allocated into 6 treatment groups, namely, a basal diet (negative control, NC), basal diet + neomycin and oxytetracycline (positive control, PC), T1 = basal diet + 0.15% postbiotic RG14 + 1.0% inulin, T2 = basal diet + 0.3% postbiotic RG14 + 1.0% inulin, T3 = basal diet + 0.45% postbiotic RG14 + 1.0% inulin, and T4 = basal diet + 0.6% postbiotic RG14 + 1.0% inulin, and fed for 6 weeks. The results showed that birds fed T1 and T3 diets had higher (P  0.05) among diets. The NC birds had higher (P
    Matched MeSH terms: Cytokines/metabolism
  14. Fulltext The NOD-like receptor signalling pathway in Helicobacter pylori infection and related gastric cancer: a case-control study and gene expression analyses
    Castaño-Rodríguez N, Kaakoush NO, Goh KL, Fock KM, Mitchell HM
    PLoS One, 2014;9(6):e98899.
    PMID: 24901306 DOI: 10.1371/journal.pone.0098899
    Currently, it is well established that cancer arises in chronically inflamed tissue. A number of NOD-like receptors (NLRs) form inflammasomes, intracellular multiprotein complexes critical for generating mature pro-inflammatory cytokines (IL-1β and IL-18). As chronic inflammation of the gastric mucosa is a consequence of Helicobacter pylori infection, we investigated the role of genetic polymorphisms and expression of genes involved in the NLR signalling pathway in H. pylori infection and related gastric cancer (GC).
    Matched MeSH terms: Cytokines/metabolism
  15. Fulltext Lack of clinical manifestations in asymptomatic dengue infection is attributed to broad down-regulation and selective up-regulation of host defence response genes
    Yeo AS, Azhar NA, Yeow W, Talbot CC, Khan MA, Shankar EM, et al.
    PLoS One, 2014;9(4):e92240.
    PMID: 24727912 DOI: 10.1371/journal.pone.0092240
    Dengue represents one of the most serious life-threatening vector-borne infectious diseases that afflicts approximately 50 million people across the globe annually. Whilst symptomatic infections are frequently reported, asymptomatic dengue remains largely unnoticed. Therefore, we sought to investigate the immune correlates conferring protection to individuals that remain clinically asymptomatic.
    Matched MeSH terms: Cytokines/metabolism
  16. Fulltext Nasal epithelial cells can act as a physiological surrogate for paediatric asthma studies
    Thavagnanam S, Parker JC, McBrien ME, Skibinski G, Shields MD, Heaney LG
    PLoS One, 2014;9(1):e85802.
    PMID: 24475053 DOI: 10.1371/journal.pone.0085802
    Differentiated paediatric epithelial cells can be used to study the role of epithelial cells in asthma. Nasal epithelial cells are easier to obtain and may act as a surrogate for bronchial epithelium in asthma studies. We assessed the suitability of nasal epithelium from asthmatic children to be a surrogate for bronchial epithelium using air-liquid interface cultures.
    Matched MeSH terms: Cytokines/metabolism
  17. Fulltext In vitro and in vivo anti-inflammatory activity of 17-O-acetylacuminolide through the inhibition of cytokines, NF-κB translocation and IKKβ activity
    Achoui M, Appleton D, Abdulla MA, Awang K, Mohd MA, Mustafa MR
    PLoS One, 2010;5(12):e15105.
    PMID: 21152019 DOI: 10.1371/journal.pone.0015105
    17-O-acetylacuminolide (AA), a diterpenoid labdane, was isolated for the first time from the plant species Neouvaria foetida. The anti-inflammatory effects of this compound were studied both in vitro and in vivo.
    Matched MeSH terms: Cytokines/metabolism*
  18. Fulltext Identification of Four-Jointed Box 1 (FJX1)-Specific Peptides for Immunotherapy of Nasopharyngeal Carcinoma
    Chai SJ, Yap YY, Foo YC, Yap LF, Ponniah S, Teo SH, et al.
    PLoS One, 2015;10(11):e0130464.
    PMID: 26536470 DOI: 10.1371/journal.pone.0130464
    Nasopharyngeal carcinoma (NPC) is highly prevalent in South East Asia and China. The poor outcome is due to late presentation, recurrence, distant metastasis and limited therapeutic options. For improved treatment outcome, immunotherapeutic approaches focusing on dendritic and autologous cytotoxic T-cell based therapies have been developed, but cost and infrastructure remain barriers for implementing these in low-resource settings. As our prior observations had found that four-jointed box 1 (FJX1), a tumor antigen, is overexpressed in NPCs, we investigated if short 9-20 amino acid sequence specific peptides matching to FJX1 requiring only intramuscular immunization to train host immune systems would be a better treatment option for this disease. Thus, we designed 8 FJX1-specific peptides and implemented an assay system to first, assess the binding of these peptides to HLA-A2 molecules on T2 cells. After, ELISPOT assays were used to determine the peptides immunogenicity and ability to induce potential cytotoxicity activity towards cancer cells. Also, T-cell proliferation assay was used to evaluate the potential of MHC class II peptides to stimulate the expansion of isolated T-cells. Our results demonstrate that these peptides are immunogenic and peptide stimulated T-cells were able to induce peptide-specific cytolytic activity specifically against FJX1-expressing cancer cells. In addition, we demonstrated that the MHC class II peptides were capable of inducing T-cell proliferation. Our results suggest that these peptides are capable of inducing specific cytotoxic cytokines secretion against FJX1-expressing cancer cells and serve as a potential vaccine-based therapy for NPC patients.
    Matched MeSH terms: Cytokines/metabolism
  19. Fulltext The anti-neuroinflammatory effects of Clinacanthus nutans leaf extract on metabolism elucidated through 1H NMR in correlation with cytokines microarray
    Ahmad Azam A, Ismail IS, Kumari Y, Shaikh MF, Abas F, Shaari K
    PLoS One, 2020;15(9):e0238503.
    PMID: 32925968 DOI: 10.1371/journal.pone.0238503
    Clinacanthus nutans (CN) (Acanthaceae) is well-known for its anti-inflammatory properties among Asian communities; however, there are currently no data specifically focused on the anti-inflammatory effects of CN on the brain tissue. Neuroinflammation is a common consequence of toxin intrusion to any part of the central nervous system (CNS). As an innate immune response, the CNS may react through both protective and/or toxic actions due to the activation of neuron cells producing pro- and/or anti-inflammatory cytokines in the brain. The unresolved activation of the inflammatory cytokines' response is associated with the pathogenesis of neurological disorders. The present study aimed to decipher the metabolic mechanism on the effects of 14 days oral treatment with CN aqueous extract in induced-lipopolysaccharides (LPS) rats through 1H NMR spectroscopic biomarker profiling of the brain tissue and the related cytokines. Based on the principal component analysis (PCA) of the nuclear magnetic resonance (NMR) spectral data, twenty-one metabolites in the brain tissue were profiled as biomarkers for the LPS (10 μL)-induced neuroinflammation following intracerebroventricular injection. Among the twenty-one biomarkers in the neuroinflammed rats, CN treatment of 1000 and 500 mg/kg BW successfully altered lactate, pyruvate, phosphorylcholine, glutamine, and α-ketoglutarate when compared to the negative control. Likewise, statistical isolinear multiple component analysis (SIMCA) showed that treatments by CN and the positive control drug, dextromethorphan (DXM, 5 mg/kg BW), have anti-neuroinflammatory potential. A moderate correlation, in the orthogonal partial least squares (OPLS) regression model, was found between the spectral metabolite profile and the cytokine levels. The current study revealed the existence of high levels of pro-inflammatory cytokines, namely IL-1α, IL-1β, and TNF-α in LPS-induced rats. Both CN dose treatments lowered IL-1β significantly better than DXM Interestingly, DXM and CN treatments both exhibited the upregulation of the anti-inflammatory cytokines IL-2 and 4. However, DXM has an advantage over CN in that the former also increased the expression of IL-10 of anti-inflammatory cytokines. In this study, a metabolomics approach was successfully applied to discover the mechanistic role of CN in controlling the neuroinflammatory conditions through the modulation of complex metabolite interactions in the rat brain.
    Matched MeSH terms: Cytokines/metabolism*
  20. Fulltext Correlation of host inflammatory cytokines and immune-related metabolites, but not viral NS1 protein, with disease severity of dengue virus infection
    Soe HJ, Manikam R, Raju CS, Khan MA, Sekaran SD
    PLoS One, 2020;15(8):e0237141.
    PMID: 32764789 DOI: 10.1371/journal.pone.0237141
    Severe dengue can be lethal caused by manifestations such as severe bleeding, fluid accumulation and organ impairment. This study aimed to investigate the role of dengue non-structural 1 (NS1) protein and host factors contributing to severe dengue. Electrical cell-substrate impedance sensing system was used to investigate the changes in barrier function of microvascular endothelial cells treated NS1 protein and serum samples from patients with different disease severity. Cytokines and metabolites profiles were assessed using a multiplex cytokine assay and liquid chromatography mass spectrometry respectively. The findings showed that NS1 was able to induce the loss of barrier function in microvascular endothelium in a dose dependent manner, however, the level of NS1 in serum samples did not correlate with the extent of vascular leakage induced. Further assessment of host factors revealed that cytokines such as CCL2, CCL5, CCL20 and CXCL1, as well as adhesion molecule ICAM-1, that are involved in leukocytes infiltration were expressed higher in dengue patients in comparison to healthy individuals. In addition, metabolomics study revealed the presence of deregulated metabolites involved in the phospholipid metabolism pathway in patients with severe manifestations. In conclusion, disease severity in dengue virus infection did not correlate directly with NS1 level, but instead with host factors that are involved in the regulation of junctional integrity and phospholipid metabolism. However, as the studied population was relatively small in this study, these exploratory findings should be confirmed by expanding the sample size using an independent cohort to further establish the significance of this study.
    Matched MeSH terms: Cytokines/metabolism
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