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Fulltext Transcriptome profiling of monocytes from XLA patients revealed the innate immune function dysregulation due to the BTK gene expression deficiency

Mirsafian H, Ripen AM, Leong WM, Chear CT, Bin Mohamad S, Merican AF

Sci Rep, 2017 07 28;7(1):6836.
PMID: 28754963 DOI: 10.1038/s41598-017-06342-5

X-linked agammaglobulinemia (XLA) is a rare genetic disorder, caused by mutations in BTK (Bruton's Tyrosine Kinase) gene. Deep high-throughput RNA sequencing (RNA-Seq) approach was utilized to explore the possible differences in transcriptome profiles of primary monocytes in XLA patients compared with healthy subjects. Our analysis revealed the differences in expression of 1,827 protein-coding genes, 95 annotated long non-coding RNAs (lncRNAs) and 20 novel lincRNAs between XLA patients and healthy subjects. GO and KEGG pathway analysis of differentially expressed (DE) protein-coding genes showed downregulation of several innate immune-related genes and upregulation of oxidative phosphorylation and apoptosis-related genes in XLA patients compared to the healthy subjects. Moreover, the functional prediction analysis of DE lncRNAs revealed their potential role in regulating the monocytes cell cycle and apoptosis in XLA patients. Our results suggested that BTK mutations may contribute to the dysregulation of innate immune system and increase susceptibility to apoptosis in monocytes of XLA patients. This study provides significant finding on the regulation of BTK gene in monocytes and the potential for development of innovative biomarkers and therapeutic monitoring strategies to increase the quality of life in XLA patients.

Matched MeSH terms: Monocytes/metabolism
Fulltext Comparison by electron microscopy of intracellular events and survival of Burkholderia pseudomallei in monocytes from normal subjects and patients with melioidosis

Puthucheary SD, Nathan SA

Singapore Med J, 2006 Aug;47(8):697-703.
PMID: 16865211

Burkholderia pseudomallei (B. pseudomallei) has been shown to persist intracellularly in patients with melioidosis, until reactivated by decreasing immunocompetence. We have previously demonstrated by transmission electron microscopy, the internalisation of B. pseudomallei by human macrophages and the occurrence of phagosome-lysosome fusion.

Matched MeSH terms: Monocytes/microbiology*
Fulltext In vitro study of Nigella sativa and thymoquinone activity on endothelial activation and monocyte adhesion

Yuhainis Firus Khan A, Mohtar F, Rahman TA, Muid SA, Froemming GRA, Nawawi H

J Appl Biomed, 2023 Jun;21(2):73-79.
PMID: 37212154 DOI: 10.32725/jab.2023.006

INTRODUCTION: Thymoquinone (TQ) is one of the bioactive compounds in Nigella sativa (NS). Also known as black seeds/cumin, it has been postulated to possess anti-atherogenic properties. However, research on the effects of NS oil (NSO) and TQ on atherogenesis remain scarce. The aim of this study is to determine gene and protein expression of Intercellular Adhesion Molecule-1 (ICAM-1), Vascular Cell Adhesion Molecule-1 (VCAM-1), and Endothelial-eukocyte adhesion molecule (E-selectin) in Human Coronary Artery Endothelial Cells (HCAECs).
METHODS: HCAECs were stimulated for 24 hours (h) with 200 µg/ml of Lipopolysaccharides (LPS) and different concentrations of NSO (55, 110, 220, 440 µg/ml) or TQ (4.5, 9.0, 18.0, 36.0 µm). The effects of NSO and TQ on gene and protein expressions were measured using multiplex gene assay and ELISA assay, respectively. Rose Bengal assay was used to analyse monocyte binding activity.
RESULTS: NSO and TQ significantly reduced ICAM-1 and VCAM-1 gene and protein expressions. TQ showed significant reduction activity of the biomarkers in dose dependent manner. HCAECs pre-treated with NSO and TQ for 24 h significantly lowered monocytes adherence compared to non-treated HCAECs.
CONCLUSIONS: NSO and TQ supplementation have anti-atherogenic properties and inhibit monocytes' adherence to HCAECs via down-regulation of ICAM-1 expression. NSO could potentially be incorporated in standard treatment regimens to prevent atherosclerosis and its related complications.

Matched MeSH terms: Monocytes*
Fulltext Dengue virus type 2 (DENV2)-induced oxidative responses in monocytes from glucose-6-phosphate dehydrogenase (G6PD)-deficient and G6PD normal subjects

Al-Alimi AA, Ali SA, Al-Hassan FM, Idris FM, Teow SY, Mohd Yusoff N

PLoS Negl Trop Dis, 2014 Mar;8(3):e2711.
PMID: 24625456 DOI: 10.1371/journal.pntd.0002711

Dengue virus is endemic in peninsular Malaysia. The clinical manifestations vary depending on the incubation period of the virus as well as the immunity of the patients. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is prevalent in Malaysia where the incidence is 3.2%. It has been noted that some G6PD-deficient individuals suffer from more severe clinical presentation of dengue infection. In this study, we aim to investigate the oxidative responses of DENV2-infected monocytes from G6PD-deficient individuals.

Matched MeSH terms: Monocytes/immunology*; Monocytes/virology*
Fulltext Blood haematology, serum thyroid hormones and glutathione peroxidase status in kacang goats fed inorganic iodine and selenium supplemented diets

Aghwan ZA, Sazili AQ, Alimon AR, Goh YM, Hilmi M

Asian-Australas J Anim Sci, 2013 Nov;26(11):1577-82.
PMID: 25049744 DOI: 10.5713/ajas.2013.13180

The effects of dietary supplementation of selenium (Se), iodine (I), and a combination of both on the blood haematology, serum free thyroxine (FT4) and free triiodothyronine (FT3) hormones and glutathione peroxidase enzyme (GSH-Px) activity were examined on twenty four (7 to 8 months old, 22±1.17 kg live weight) Kacang crossbred male goats. Animals were randomly assigned to four dietary treatments (6 animals in each group). Throughout 100 d of feeding trial, the animals of control group (CON) received a basal diet, while the other three groups were offered basal diet supplemented with 0.6 mg/kg diet DM Se (SS), or 0.6 mg/kg diet DM I (PI), or a combination of both Se and I, each at 0.6 mg/kg diet DM (SSPI). The haematological attributes which are haemoglobin (Hb), red blood cell (RBC), packed cell volume (PCV), mean cell volume (MCV), white blood cells (WBC), band neutrophils (B Neut), segmented neutrophils (S Neut), lymphocytes (Lymph), monocytes (Mono), eosinophils (Eosin) and basophils (Baso) were similar among the four treatment groups, while serum levels of Se and I increased significantly (p<0.05) in the supplemented groups. The combined dietary supplementation of Se and I (SSPI) significantly increased serum FT3 in the supplemented animals. Serum GSH-Px activity increased significantly in the animals of SS and SSPI groups. It is concluded that the dietary supplementation of inorganic Se and I at a level of 0.6 mg/kg DM increased serum Se and I concentration, FT3 hormone and GSH-Px activity of Kacang crossbred male goats.

Matched MeSH terms: Monocytes
Cardamonin, inhibits pro-inflammatory mediators in activated RAW 264.7 cells and whole blood

Ahmad S, Israf DA, Lajis NH, Shaari K, Mohamed H, Wahab AA, et al.

Eur J Pharmacol, 2006 May 24;538(1-3):188-94.
PMID: 16650843

Some chalcones, such as hydroxychalcones have been reported previously to inhibit major pro-inflammatory mediators such as nitric oxide (NO), prostaglandin E(2) (PGE(2)), tumor necrosis factor-alpha (TNF-alpha) and reactive oxygen species production by suppressing inducible enzyme expression via inhibition of the mitogen-activated protein kinase (MAPK) pathway and nuclear translocation of critical transcription factors. In this report, the effects of cardamonin (2',4'-dihydroxy-6'-methoxychalcone), a chalcone that we have previously isolated from Alpinia rafflesiana, was evaluated upon two cellular systems that are repeatedly used in the analysis of anti-inflammatory bioactive compounds namely RAW 264.7 cells and whole blood. Cardamonin inhibited NO and PGE(2) production from lipopolysaccharide- and interferon-gamma-induced RAW cells and whole blood with IC(50) values of 11.4 microM and 26.8 microM, respectively. Analysis of thromboxane B(2) (TxB(2)) secretion from whole blood either stimulated via the COX-1 or COX-2 pathway revealed that cardamonin inhibits the generation of TxB(2) via both pathways with IC(50) values of 2.9 and 1.1 microM, respectively. Analysis of IC(50) ratios determined that cardamonin was more COX-2 selective in its inhibition of TxB(2) with a ratio of 0.39. Cardamonin also inhibited the generation of intracellular reactive oxygen species and secretion of TNF-alpha from RAW 264.7 cells in a dose responsive manner with IC(50) values of 12.8 microM and 4.6 microM, respectively. However, cardamonin was a moderate inhibitor of lipoxygenase activity when tested in an enzymatic assay system, in which not a single concentration tested was able to cause an inhibition of more than 50%. Our results suggest that cardamonin acts upon major pro-inflammatory mediators in a similar fashion as described by previous work on other closely related synthetic hydroxychalcones and strengthens the conclusion of the importance of the methoxyl moiety substitution on the 4' or 6' locations of the A benzene ring.

Matched MeSH terms: Monocytes/cytology; Monocytes/drug effects; Monocytes/metabolism
Fulltext Novel piperazine core compound induces death in human liver cancer cells: possible pharmacological properties

Samie N, Muniandy S, Kanthimathi MS, Haerian BS, Azudin RE

Sci Rep, 2016 Apr 13;6:24172.
PMID: 27072064 DOI: 10.1038/srep24172

The current study evaluates the cytotoxic mechanism of a novel piperazine derivate designated as PCC against human liver cancer cells. In this context, human liver cancer cell lines, SNU-475 and 243, human monocyte/macrophage cell line, CRL-9855, and human B lymphocyte cell line, CCL-156, were used to determine the IC50 of PCC using the standard MTT assay. PCC displayed a strong suppressive effect on SNU-475 and SNU-423 cells with an IC50 value of 6.98 ± 0.11 μg/ml and 7.76 ± 0.45 μg/ml respectively, after 24 h of treatment. Significant dipping in the mitochondrial membrane potential and elevation in the released of cytochrome c from the mitochondria indicated the induction of the intrinsic apoptosis pathway by PCC. Activation of this pathway was further evidenced by significant activation of caspase 3/7 and 9. PCC was also shown to activate the extrinsic pathways of apoptosis via activation of caspase-8 which is linked to the suppression of NF-ƙB translocation to the nucleus. Cell cycle arrest in the G1 phase was confirmed by flow cytometry and up-regulation of glutathione reductase expression was quantified by qPCR. This study suggests that PCC is a simultaneous inducer of intrinsic and extrinsic pathways of apoptosis in liver cancer cell lines.

Matched MeSH terms: Monocytes
Fulltext Serum neopterin is elevated in patients infected with Shigella

Singh KK, Wan-Nurfahizul-Izzati W, Ismail A

Gut Pathog, 2010;2(1):9.
PMID: 20727206 DOI: 10.1186/1757-4749-2-9

Neopterin is produced by human macrophages/monocytes when stimulated with interferon-gamma. Production of neopterin is found in serum, cerebrospinal fluid (CSF) and urine of patients with infections by viruses, intracellular bacteria and parasites, autoimmune diseases, malignant tumors and patients in allograft rejection episodes.

Matched MeSH terms: Monocytes
Fulltext Clinical utility of extended monocytes parameters as a screening tool in suspected dengue infection

Nur Aliaa, Eusni Rahayu Mohd Tohit, Nik Hafidzah Nik Mustapha, Malina Osman

Malaysian Journal of Medicine and Health Sciences, 2020;16(1):162-167.
MyJurnal

Introduction: Increased monocyte percentage and monocyte anisocytosis were suggested as new markers for den- gue fever detection. This study aims to investigate and evaluate monocyte volume standard deviation (MoV-SD) and monocyte percentage (Mono %) parameters using Coulter automated haematology analyser as screening parameters in discriminating between dengue infection and other febrile illness. Methods: A cross-sectional laboratory analysis using suspected dengue fever patients were included in this study. The study was conducted in the Department of Pathology, Hospital Tuanku Jaafar Seremban from June 2016 until June 2017. Patients were classified into dengue positive and dengue negative based on dengue IgM and NS1 result. The diagnostic performance of MoV-SD and Mono % was analysed by receiver operating characteristic (ROC) curve analysis. The cut-off value of the MoV-SD and Mono % was determined and evaluated with the validation group. Chi-square test was used to assess the as- sociation between the parameters. Results: 88 (48.4%) from 182 samples were confirmed to have dengue infection. ROC curve analysis showed Mono % at cut off value of 10.5 % with area under the curve (AUC) of 0.869 with 84.1% sensitivity and 84% specificity (95% CI: 0.812-0.925) and MoV-SD cut off value at 22.2 (AUC 0.776, 80.7% sensitivity, 61.7% specificity, 95% CI: 0.709-0.843) are an excellent parameters in separating dengue positive and dengue-negative patients. A cut-off value of 10.5 of Mono % and 22.2 of MoV-SD were applied to the validation group showed 83.1%, 66.4% sensitivity and 84.9%, 77.3% specificity respectively. Conclusion: MoV-SD and Mono
% parameters are a potential parameter for the screening of dengue infection in acute febrile illness patients with good specificity and sensitivity.

Matched MeSH terms: Monocytes
Fulltext Activin a: its role and involvement in inflammatory diseases

Tie, Tung Hing, Rusliza Basir, Chuah, Yaw Kuang, Herni Talib, Norshariza Nordin

Pertanika Journal of Science & Technology, 2015;23(2):163-176.
MyJurnal

Activin proteins are members of the transforming growth factor-β family. Activin A is involved in several biological responses including wound repair, cell death, proliferation and differentiation of many cell types. Biologically active activins consist of homodimers or heterodimers of two beta (β) subunits that are linked together by a single covalent disulphide bond. The subunits in humans are βA, βB, βC and βE. As an example, a combination of two βA subunits will produce a unit of activin A. These proteins are found in most cells of body such as macrophage and activated circulating monocytes. Their role in inflammation can be categorised into two types, either pro- or anti-inflammatory agents, depending on the cell type and phase. Activin signals are kept in balance by antagonist follistatin (Fst), which is a glycoprotein expressed in tissues and encoded by the follistatin gene in humans.

Matched MeSH terms: Monocytes
Fulltext Immunosuppressive Effects of Natural α,β-Unsaturated Carbonyl-Based Compounds, and Their Analogs and Derivatives, on Immune Cells: A Review

Arshad L, Jantan I, Bukhari SN, Haque MA

Front Pharmacol, 2017;8:22.
PMID: 28194110 DOI: 10.3389/fphar.2017.00022

The immune system is complex and pervasive as it functions to prevent or limit infections in the human body. In a healthy organism, the immune system and the redox balance of immune cells maintain homeostasis within the body. The failure to maintain the balance may lead to impaired immune response and either over activity or abnormally low activity of the immune cells resulting in autoimmune or immune deficiency diseases. Compounds containing α,β-unsaturated carbonyl-based moieties are often reactive. The reactivity of these groups is responsible for their diverse pharmacological activities, and the most important and widely studied include the natural compounds curcumin, chalcone, and zerumbone. Numerous studies have revealed the mainly immunosuppressive and anti-inflammatory activities of the aforesaid compounds. This review highlights the specific immunosuppressive effects of these natural α,β-unsaturated carbonyl-based compounds, and their analogs and derivatives on different types of immune cells of the innate (granulocytes, monocytes, macrophages, and dendritic cells) and adaptive (T cells, B cells, and natural killer cells) immune systems. The inhibitory effects of these compounds have been comprehensively studied on neutrophils, monocytes and macrophages but their effects on T cells, B cells, natural killer cells, and dendritic cells have not been well investigated. It is of paramount importance to continue generating experimental data on the mechanisms of action of α,β-unsaturated carbonyl-based compounds on immune cells to provide useful information for ensuing research to discover new immunomodulating agents.

Matched MeSH terms: Monocytes
Maslinic acid suppresses macrophage foam cells formation: Regulation of monocyte recruitment and macrophage lipids homeostasis

Phang SW, Ooi BK, Ahemad N, Yap WH

Vascul Pharmacol, 2020 03 19;128-129:106675.
PMID: 32200116 DOI: 10.1016/j.vph.2020.106675

The transformation of macrophages to foam cells is a critical component in atherosclerotic lesion formation. Maslinic acid (MA), a novel natural pentacyclic triterpene, has cardioprotective and anti-inflammatory properties. It is hypothesized that MA can suppress monocyte recruitment to endothelial cells and inhibit macrophage foam cells formation. Previous study shows that MA inhibits inflammatory effects induced by sPLA2-IIA, including foam cells formation. This study elucidates the regulatory effect of MA in monocyte recruitment, macrophage lipid accumulation and cholesterol efflux. Our findings demonstrate that MA inhibits THP-1 monocyte adhesion to HUVEC cells in a TNFα-dependent and independent manner, but it induces trans-endothelial migration marginally at low concentration. MA down-regulates both gene and protein expression on VCAM-1 and MCP-1 in HUVECs. We further showed that MA suppresses macrophage foam cells formation, as indicated from the Oil-Red-O staining and flow cytometric analysis of intracellular lipids accumulation. The effects observed may be attributed to the antioxidant properties of MA where it was shown to suppress CuSO4-induced lipid peroxidation. MA inhibits scavenger receptors SR-A and CD36 expression while enhancing cholesterol efflux. MA enhances cholesterol efflux transporters ABCA1 and ABCG1 genes expression marginally without inducing its protein expression. In this study, MA was shown to target important steps that contribute to foam cell formation, including its ability in reducing monocytes adhesion to endothelial cells and LDL peroxidation, down-regulating scavenger receptors expression as well as enhancing cholesterol efflux, which might be of great importance in the context of atherosclerosis prevention and treatment.

Matched MeSH terms: Monocytes
Fulltext The CD14 C-260T single nucleotide polymorphism (SNP) modulates monocyte/macrophage activation in treated HIV-infected individuals

Rajasuriar R, Kong YY, Nadarajah R, Abdullah NK, Spelman T, Yuhana MY, et al.

J Transl Med, 2015;13:30.
PMID: 25622527 DOI: 10.1186/s12967-015-0391-6

HIV-infected individuals have an increased risk of cardiovascular disease (CVD). T-allele carriers of the CD14 C-260T single-nucleotide polymorphism (SNP) have reported increased expression of the LPS-binding receptor, CD14 and inflammation in the general population. Our aim was to explore the relationship of this SNP with monocyte/macrophage activation and inflammation and its association with sub-clinical atherosclerosis in HIV-infected individuals.

Matched MeSH terms: Monocytes/metabolism*
Chediak-Higashi syndrome: a case report

Jayaranee S, Menaka N

Malays J Pathol, 2004 Jun;26(1):53-7.
PMID: 16190108

A 5-month-old Chinese male infant was referred to the University Hospital, Kuala Lumpur for persistent fever, generalised rash and abdominal distension. Clinically he was suspected to have haemophagocytic lymphohistiocytosis. Haematological findings including the presence of several abnormal giant granules in neutrophils and single large azurophilic granules in many lymphocytes and monocytes in the peripheral blood established the diagnosis of Chediak-Higashi syndrome. The patient responded to allogeneic bone marrow transplant. This paper discusses the characteristic features, clinical course and management of this rare disorder. We suggest that peripheral blood film examination for the abnormal giant granules in granulocytes is an essential investigation in all young children with frequent recurrent infections or who are suspected to have virus-associated haemophagocytic syndrome or familial haemophagocytic lymphohistiocytosis.

Matched MeSH terms: Monocytes/pathology
Fulltext Uvulo-palatoglossal junctional ulcers--an early clinical sign of exanthem subitum due to human herpesvirus 6

Chua KB, Lam SK, Sazaly AB, Lim ST, Paranjothy M

Med J Malaysia, 1999 Mar;54(1):32-6.
PMID: 10972002

A provisional clinical diagnosis of exanthem subitum was made in six febrile infants seen in the Paediatric Unit of Assunta Hospital, Petaling Jaya, Malaysia with uvulo-palatoglossal junctional ulcers prior to the eruption of maculopapular rash. On follow-up, all six infants developed maculopapular rash with the subsidence of fever at the end of the fourth febrile day. Human herpesvirus 6 was isolated from the peripheral blood mononuclear cells during the acute phase of the illness and HHV 6 specific genome was also detected in these cells by nested polymerase chain reaction. All the six infants showed seroconversion for both specific IgG and IgM to the isolated virus. This study suggests that the presence of uvulo-palatoglossal junctional ulcers could be a useful early clinical sign of exanthem subitum due to human herpesvirus 6.

Matched MeSH terms: Monocytes/pathology
Fulltext Human mesenchymal stem cells inhibit the differentiation and effector functions of monocytes

Maqbool M, Algraittee SJR, Boroojerdi MH, Sarmadi VH, John CM, Vidyadaran S, et al.

Innate Immun, 2020 07;26(5):424-434.
PMID: 32635840 DOI: 10.1177/1753425919899132

Although monocytes represent an essential part of the host defence system, their accumulation and prolonged stimulation could be detrimental and may aggravate chronic inflammatory diseases. The present study has explored the less-understood immunomodulatory effects of mesenchymal stem cells on monocyte functions. Isolated purified human monocytes were co-cultured with human umbilical cord-derived mesenchymal stem cells under appropriate culture conditions to assess monocytes' vital functions. Based on the surface marker analysis, mesenchymal stem cells halted monocyte differentiation into dendritic cells and macrophages and reduced their phagocytosis functions, which rendered an inability to stimulate T-cell proliferation. The present study confers that mesenchymal stem cells exerted potent immunosuppressive activity on monocyte functions such as differentiation, phagocytosis and Ag presentation; hence, they promise a potential therapeutic role in down-regulating the unwanted monocyte-mediated immune responses in the context of chronic inflammatory diseases.

Matched MeSH terms: Monocytes/immunology*
Quantification of human PPARgamma1 gene expression by competitive PCR using an homologous internal standard

Yaacob NS, Bakar RA, Norazmi MN

Ann Clin Lab Sci, 2004;34(1):47-56.
PMID: 15038667

The polymerase chain reaction (PCR) is useful for amplifying specific mRNAs, particularly those present in low copy numbers. However, due to the exponential nature of the amplification process, PCR cannot readily be used to quantify gene expression. A competitive PCR technique was developed to address this shortcoming. An internal standard that is 100% homologous to, but shorter than, the target gene was constructed. The practicality of the method was demonstrated by determining the expression levels of a human transcription factor, peroxisome proliferator-activated receptor gamma 1 (hPPARgamma1) which is normally present in low copy numbers in selected cells. A mock system was used to test the accuracy and sensitivity of the method, which was subsequently used to determine the expression of this receptor in lipopolysaccharide (LPS)-activated monocytes, which are known to express hPPARgamma1 differentially during cellular activation. Densitometric analysis showed that the competitive PCR method reliably estimated the expression levels of hPPARgamma1 at the attomole (10(-18)) level in monocytes.

Matched MeSH terms: Monocytes/chemistry
Fulltext Persistent infection due to a small-colony variant of Burkholderia pseudomallei leads to PD-1 upregulation on circulating immune cells and mononuclear infiltration in viscera of experimental BALB/c mice

See JX, Chandramathi S, Abdulla MA, Vadivelu J, Shankar EM

PLoS Negl Trop Dis, 2017 Aug;11(8):e0005702.
PMID: 28820897 DOI: 10.1371/journal.pntd.0005702

BACKGROUND: Melioidosis is a neglected tropical disease endemic across South East Asia and Northern Australia. The etiological agent, Burkholderia pseudomallei (B.pseudomallei), is a Gram-negative, rod-shaped, motile bacterium residing in the soil and muddy water across endemic regions of the tropical world. The bacterium is known to cause persistent infections by remaining latent within host cells for prolonged duration. Reactivation of the recrudescent disease often occurs in elders whose immunity wanes. Moreover, recurrence rates in melioidosis patients can be up to ~13% despite appropriate antibiotic therapy, suggestive of bacterial persistence and inefficacy of antibiotic regimens. The mechanisms behind bacterial persistence in the host remain unclear, and hence understanding host immunity during persistent B. pseudomallei infections may help designing potential immunotherapy.
METHODOLOGY/PRINCIPAL FINDINGS: A persistent infection was generated using a small-colony variant (SCV) and a wild-type (WT) B. pseudomallei in BALB/c mice via intranasal administration. Infected mice that survived for >60 days were sacrificed. Lungs, livers, spleens, and peripheral blood mononuclear cells were harvested for experimental investigations. Histopathological changes of organs were observed in the infected mice, suggestive of successful establishment of persistent infections. Moreover, natural killer (NK) cell frequency was increased in SCV- and WT-infected mice. We observed programmed death-1 (PD-1) upregulation on B cells of SCV- and WT-infected mice. Interestingly, PD-1 upregulation was only observed on NK cells and monocytes of SCV-infected mice. In contrast, cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) downregulation was seen on NK cells of WT-infected mice, and on monocytes of SCV- and WT-infected mice.
CONCLUSIONS/SIGNIFICANCE: The SCV and the WT of B. pseudomallei distinctly upregulated PD-1 expression on B cells, NK cells, and monocytes to dampen host immunity, which likely facilitates bacterial persistence. PD-1/PD-L1 pathway appears to play an important role in the persistence of B. pseudomallei in the host.

Matched MeSH terms: Monocytes/chemistry
Toward a Reference Gene Catalog of Human Primary Monocytes

Mirsafian H, Ripen AM, Manaharan T, Mohamad SB, Merican AF

OMICS, 2016 11;20(11):627-634.
PMID: 27828772

Transcriptome analyses based on high-throughput RNA sequencing (RNA-Seq) provide powerful and quantitative characterization of cell types and in-depth understanding of biological systems in health and disease. In this study, we present a comprehensive transcriptome profile of human primary monocytes, a crucial component of the innate immune system. We performed deep RNA-Seq of monocytes from six healthy subjects and integrated our data with 10 other publicly available RNA-Seq datasets of human monocytes. A total of 1.9 billion reads were generated, which allowed us to capture most of the genes transcribed in human monocytes, including 11,994 protein-coding genes, 5558 noncoding genes (including long noncoding RNAs, precursor miRNAs, and others), 2819 pseudogenes, and 7034 putative novel transcripts. In addition, we profiled the expression pattern of 1155 transcription factors (TFs) in human monocytes, which are the main molecules in controlling the gene transcription. An interaction network was constructed among the top expressed TFs and their targeted genes, which revealed the potential key regulatory genes in biological function of human monocytes. The gene catalog of human primary monocytes provided in this study offers significant promise and future potential clinical applications in the fields of precision medicine, systems diagnostics, immunogenomics, and the development of innovative biomarkers and therapeutic monitoring strategies.

Matched MeSH terms: Monocytes/metabolism*
The synthetic curcuminoid BHMC restores endotoxin-stimulated HUVEC dysfunction:Specific disruption on enzymatic activity of p38 MAPK

Tham CL, Hazeera Harith H, Wai Lam K, Joong Chong Y, Singh Cheema M, Roslan Sulaiman M, et al.

Eur J Pharmacol, 2015 Feb 15;749:1-11.
PMID: 25560198 DOI: 10.1016/j.ejphar.2014.12.015

2,6-bis-(4-hydroxyl-3-methoxybenzylidine)cyclohexanone (BHMC) has been proven to selectively inhibit the synthesis of proinflammatory mediators in lipopolysaccharide-induced U937 monocytes through specific interruption of p38 Mitogen-Activated Protein Kinase enzymatic activity and improves the survival rate in a murine lethal sepsis model. The present study addressed the effects of BHMC upon lipopolysaccharide-induced endothelial dysfunction in human umbilical vein endothelial cells to determine the underlying mechanisms. The cytotoxicity effect of BHMC on HUVEC were determined by MTT assay. The effects of BHMC on endothelial dysfunction induced by lipopolysaccharide such as endothelial hyperpermeability, monocyte-endothelial adhesion, transendothelial migration, up-regulation of adhesion molecules and chemokines were evaluated. The effects of BHMC at transcriptional and post-translational levels were determined by Reverse Transcriptase-Polymerase Chain Reaction and Western Blots. The mode of action of BHMC was dissected by looking into the activation of Nuclear Factor-kappa B and Mitogen-Activated Protein Kinases. BHMC concentration-dependently reduced endothelial hyperpermeability, leukocyte-endothelial cell adhesion and monocyte transendothelial migration through inhibition of the protein expression of adhesion molecules (Intercellular Adhesion Molecule-1 and Vascular Cell Adhesion Molecule-1) and secretion of chemokines (Monocyte Chemotactic Protein-1) at the transcriptional level. BHMC restored endothelial dysfunction via selective inhibition of p38 Mitogen-Activated Protein Kinase enzymatic activity which indirectly prevents the activation of Nuclear Factor-kappaB and Activator Protein-1 transcription factors. These findings further support earlier observations on the inhibition of BHMC on inflammatory events through specific disruption of p38 Mitogen-Activated Protein Kinase enzymatic activity and provide new insights into the inhibitory effects of BHMC on lipopolysaccharide-induced endothelial dysfunction.

Matched MeSH terms: Monocytes/drug effects; Monocytes/physiology

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