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Arthritis Research & Therapy Sep 2022The IL-23/IL-17 axis is involved in inflammatory diseases including arthritis and psoriasis. However, the response to IL-23 or IL-17 inhibitors is different depending on...
BACKGROUND
The IL-23/IL-17 axis is involved in inflammatory diseases including arthritis and psoriasis. However, the response to IL-23 or IL-17 inhibitors is different depending on the disease. The aim was to compare the effects of interactions between immune and stromal cells on the IL-23 axis to understand these differences.
METHODS
Peripheral blood mononuclear cells were co-cultured with RA synoviocytes or Pso skin fibroblasts, with or without phytohemagglutinin, IL-23, or anti-IL-23 antibody. Production of IL-6, IL-1β, IL-23, IL-17, IL-12, and IFNγ was measured by ELISA. IL-23 and cytokine receptor gene expression (IL-17RA, IL-17RC, IL-12Rβ1, IL-12Rβ2, and IL-23R) was analyzed by RT-qPCR. IL-12Rβ1 and IL-23R subunits were analyzed by flow cytometry.
RESULTS
The production of IL-6, IL-1β, IL-17, IL-12, and IFNγ with synoviocytes or skin fibroblasts was rather similar, and cell interactions with immune cells increased their production, specifically that of IL-17. A major difference was observed for IL-23. Interactions with synoviocytes but not with skin fibroblasts decreased IL-23 secretion while mRNA level was increased, mainly with synoviocytes, reflecting a major consumption difference. IL-23 addition had only one effect, the increase of IL-17 secretion. Cell activation induced similar effects on cytokine receptor gene expression in co-cultures with synoviocytes or skin fibroblasts. The key difference was the cell interaction effects depending on the stromal cell origin. Interactions with synoviocytes increased the expression of both IL-23 receptor subunits at mRNA levels and IL-23R at the surface expression level while interactions with skin fibroblasts decreased their expression at the mRNA level and had no effect at the surface expression level.
CONCLUSION
Interactions between immune and stromal cells are crucial in cytokine production and their receptor expression. The origin of stromal cells had a major influence on the production of IL-23 and its receptor expression. Such differences may explain part of the heterogeneity in treatment response.
Topics: Arthritis, Rheumatoid; Cell Communication; Fibroblasts; Gene Expression; Humans; Interleukin-12; Interleukin-17; Interleukin-6; Leukocytes, Mononuclear; RNA, Messenger; Synoviocytes
PubMed: 36088336
DOI: 10.1186/s13075-022-02904-9 -
Journal of Traditional and... Sep 2022The immune system functions to protect the host from a broad array of infectious diseases. Here, we evaluated the immunomodulatory effects of green coffee extract...
BACKGROUND
The immune system functions to protect the host from a broad array of infectious diseases. Here, we evaluated the immunomodulatory effects of green coffee extract (GCE), and conducted a double-blinded, randomized and placebo-controlled trial among apparently healthy individuals.
METHODS
We determined the levels and functions of inflammatory and immune markers viz., phospho-NF-κB p65 ser536, chemotaxis, phagocytosis, TH1/TH2 cytokines and IgG production. We also evaluated several immunological markers such as total leukocyte counts, differential leukocyte counts, NK cell activity, CD4/CD8 ratio, serum immunoglobulin, C-reactive protein (CRP) and pro-inflammatory cytokines (IL-6 and TNF-α).
RESULTS AND CONCLUSION
GCE significantly inhibited LPS-induced NF-κB p65 ser536 phosphorylation, MCP-1-induced chemotaxis and significantly enhanced phagocytosis and IgG production. In addition, GCE modulated PMA/PHA-induced TH1/TH2 cytokine production. Clinical investigations suggested that the expression of CD56 and CD16 was markedly augmented on NK cells following GCE treatment. GCE significantly enhanced IgA production before and after influenza vaccination. Similarly, IL-6, TNF-α and CRP levels were significantly inhibited by GCE. Together, GCE confers several salubrious immunomodulatory effects at different levels attributing to optimal functioning of immune responses in the host.
TAXONOMY
Cell biology, Clinical study, Clinical Trial.
PubMed: 36081816
DOI: 10.1016/j.jtcme.2022.01.007 -
Molecular Biology Reports Oct 2022Lectins are carbohydrate-binding molecules that can bind specifically to the sugar residues of glycoconjugates and are found in almost all organisms. Plant lectins...
BACKGROUND
Lectins are carbohydrate-binding molecules that can bind specifically to the sugar residues of glycoconjugates and are found in almost all organisms. Plant lectins subjected to many studies reported exhibiting anti-cancer activity. This study aimed to investigate the possible molecular mechanisms of Maackia amurensis leukoagglutinin II (MAL-II) treated ATCCs.
METHODS AND RESULTS
We tested the effects of MAL-II, which is isolated from Amur seeds, on cancerous features of 8505C human anaplastic thyroid cancer cells (ATCCs) on a large scale using RNA-Seq. Transcriptome analysis was performed using Illumina next-generation sequencing technology by using cDNA libraries obtained from total RNA isolates of ATCCs treated with 0.25 µM MAL-II for 24 h. Gene ontology and pathway enrichment analysis were performed for the systematic analysis of gene functions. Moreover, we validated RNA-Seq findings using qPCR. Our results showed that many cancer-related genes such as TENM4, STIM2, SYT12, PIEZO2, ABCG1, SPNS2, ARRB1, and IRX5 were downregulated and many anticancer genes such as HSPA6, G0S2, TNFAIP3, GEM, GADD45G, RND1, SERPINB2, and IL24 were upregulated. Also, pathway enrichment analysis showed that differentially expressed genes were found to be associated with Ras, p53, and apoptosis signaling pathways, which are some important signal transduction pathways in development, proliferation, stem cell control, and carcinogenesis.
CONCLUSION
Collectively, our results show that MAL-II treatment reveals significant antitumor activity by changing the expression of many cancer-related genes and implies that MAL-II treatment might be a potential candidate molecule to inhibit the malignancy of human anaplastic thyroid cancer.
Topics: Glycoconjugates; Humans; Lectins; Phytohemagglutinins; Plant Lectins; RNA; RNA-Seq; Sugars; Thyroid Carcinoma, Anaplastic; Thyroid Neoplasms; Transcriptome; Tumor Suppressor Protein p53; rho GTP-Binding Proteins
PubMed: 36057880
DOI: 10.1007/s11033-022-07759-6 -
Chemosphere Nov 2022Among others, the global change involves a worldwide increase in cropland area, with the concomitant rise in nitrogenous fertilizer supplementation and species range...
Among others, the global change involves a worldwide increase in cropland area, with the concomitant rise in nitrogenous fertilizer supplementation and species range alterations, including parasites and pathogens. As most animals rely on their immune systems against these infectious agents, studying the potential effects of nitrogenous compounds on animal immune response is vital to understand their susceptibility to infections under these altered circumstances. Being subjected to an alarming process of global declines, amphibians are the object of particular attention, given their sensitivity to these compounds, especially to ammonium. Moreover, whereas adults can actively avoid polluted patches, larvae are confined within their waterbodies, thus exposed to contaminants in it. In this work, we test whether chronic exposure to a sublethal dose of ammonium during the larval stage of Pelophylax perezi frogs, released from all contamination after metamorphosis, leads to impaired inflammatory response to phytohemagglutinin in adults. We also test whether such a response differs between agrosystem individuals as compared with conspecifics from natural habitats. We found negative carryover effects of chronic exposure of larvae to ammonium on adult inflammatory response, which could imply a greater susceptibility to pathogens and parasites. However, this damage is only true for males, which, according to the immunocompetence handicap hypothesis, could be a consequence of a testosterone-triggered impairment of male immune function. In disagreement with our prediction, however, we detected no differences in the inflammatory response of agrosystem frogs to phytohemagglutinin as compared with natural habitat conspecifics.
Topics: Ammonium Compounds; Animals; Anura; Fertilizers; Larva; Male; Phytohemagglutinins; Ranidae; Testosterone; Water Pollutants, Chemical
PubMed: 36037957
DOI: 10.1016/j.chemosphere.2022.136202 -
Journal of Clinical Medicine Aug 2022Dry eye (DED) is a prevalent disease with immune-mediated inflammation as the principal pathophysiological etiology. Olive pomace, the major by-product of the olive oil...
Dry eye (DED) is a prevalent disease with immune-mediated inflammation as the principal pathophysiological etiology. Olive pomace, the major by-product of the olive oil industry, is rich in high-value polyphenols. Their anti-inflammatory and immunomodulatory activities were determined on human CD4+ T cells (hTCD4+) and in a DED animal model. The viability of hTCD4+ cells isolated from peripheral blood and activated with phytohemagglutinin-M was evaluated after treatment for 48 h with an olive pomace extract (OPT3, 0.10-0.40 mg/mL) and its major compound, hydroxytyrosol (25-100 μM). Regarding the DED animal model, 100 μM hydroxytyrosol, 0.20 mg/mL OPT3, or vehicle (borate buffer) were topically administered to 14 days-desiccating stress-exposed (constant airflow/scopolamine administration) C57BL/6 mice. Tear volume, corneal fluorescein staining (CFS), CD4+, and CD8+ T cell count in lymph nodes (flow cytometry), and and gene expression (qRT-PCR) in the cornea, conjunctiva, and lacrimal glands were evaluated. OPT3 (0.2-0.4 mg/mL) and hydroxytyrosol (100 μM) significantly reduced hTCD4+ proliferation. In mice, both treatments reduced lacrimal gland gene expression. OPT3 also decreased CFS, and conjunctival and corneal gene expression. In lymph nodes, hydroxytyrosol reduced CD3+, OPT3, and CD8+ count. Thus, a high-value application as a promising DED protection was proposed for olive pomace.
PubMed: 36012942
DOI: 10.3390/jcm11164703 -
Veterinary World Jun 2022The reports from the Ministry of Agriculture and Fisheries suggest that camels suffer less compared to goats, sheep, and cows from a number of common infectious diseases...
BACKGROUND AND AIM
The reports from the Ministry of Agriculture and Fisheries suggest that camels suffer less compared to goats, sheep, and cows from a number of common infectious diseases in Oman. However, there is no immunological evidence to substantiate this claim. This present study is, therefore, an attempt to study the immunological responses of camels, goats, sheep, and cows by comparing their oxidative respiratory burst of peripheral blood leukocytes (PBLs) as a marker of innate immunity occurring during phagocytosis and the mitogenic responses of their peripheral blood mononuclear leukocytes (PBMLs) as a marker of their adaptive immune response.
MATERIALS AND METHODS
Ten female adult animals (n = 10) were selected from each species (goats, sheep, and cows). The goats, sheep, and cows were maintained at the Agricultural Experiment Station, while camels were kept at the Royal Camel Corps (RCC). Blood samples were collected from the jugular vein in 7 mL of heparin and ethylenediaminetetraacetic acid vacutainer tubes. The oxidative respiratory burst of PBLs was measured using a chemiluminescence (CL) assay. Reactants consisted of 75 mL of whole blood diluted (1:50), 75 mL of luminol/isoluminol, and 75 mL of zymosan opsonized with non-heat inactivated serum/heat-inactivated serum or non-opsonized zymosan. CL responses were measured as relative light units and expressed as the mean count per minute and peak CL values. The mitogenic response of PBMLs to concanavalin A (Con-A), phytohemagglutinin (PHA), and pokeweed mitogen (PWM) was tested using a WST-8 assay and read spectrophotometrically at 450 nm.
RESULTS
The present findings showed that camel PBLs generate significantly higher CL responses, both intracellularly as well as extracellularly, with zymosan opsonized with autologous serum. Camel PBLs demonstrated a significantly higher (p = 0.001) response when stimulated with zymosan opsonized with heat-inactivated serum compared to those of goat, sheep, and cow lymphocytes from camels exhibited significantly higher (p = 0.001) stimulation indices (SI) with Con-A, PHA, and PWM.
CONCLUSION
The present study suggests that camels are capable of mounting both superior innate as well as adaptive immune responses and provide immunological evidence supporting the belief of some authors, who have proposed that camels are less susceptible to a number of common infectious diseases than other domesticated ruminants.
PubMed: 35993061
DOI: 10.14202/vetworld.2022.1398-1407 -
The Journal of Poultry Science Jul 2022The objective of this study was to determine the effects of dietary soy saponin (SS) on the antioxidant and immune functions of laying hens. Two hundred seventy...
The objective of this study was to determine the effects of dietary soy saponin (SS) on the antioxidant and immune functions of laying hens. Two hundred seventy 22-week-old Hy-line gray layers were randomly allocated into three treatment groups: a control group (Control) fed a basal diet with low soybean meal and groups supplemented with 50 and 500 mg/kg SS (50 SS and 500 SS). After ten weeks, eight chickens from each treatment group were anesthetized and sacrificed to collect tissue samples. In the 50 and 500 SS groups, results showed that the levels of superoxide dismutase (SOD) in serum and spleen were elevated, and the content of malondialdehyde (MDA) in serum decreased. The mRNA levels of genes such as NF-E2-related factor 2 () in the ileum and and in the spleen were also upregulated. In addition, the skin irritation index of phytohemagglutinin (PHA), the number of serum white blood cells, and lymphocytes were elevated in the two groups. At the same time, the number of monocytes in the blood increased in the 50 SS group, and it was significantly higher in the 500 SS group. In addition, the mRNA levels of lysozyme () and in the spleen were upregulated, similar to the mRNA levels of zinc finger protein A20 () in the ileum. Furthermore, the mRNA levels of and in the ileum were downregulated. In conclusion, with supplementation of 50 and 500 mg/kg SS in low soybean meal diets, the antioxidant, and immune functions of laying hens were improved. More importantly, the target for SS to exert biological effects on laying hens may be in the intestine and spleen tissues.
PubMed: 35989694
DOI: 10.2141/jpsa.0210073 -
Radiation Oncology (London, England) Aug 2022As one of the most common chromosomal causes, chromosome translocation leads to T-cell acute lymphoblastic leukemia (T-ALL). Ku70 is one of the key factors of...
BACKGROUND
As one of the most common chromosomal causes, chromosome translocation leads to T-cell acute lymphoblastic leukemia (T-ALL). Ku70 is one of the key factors of error-prone DNA repair and it may end in translocation. So far, the direct correlation between Ku70 and translocation has not been assessed. This study aimed to investigate the association between Ku70 and translocation in human lymphocytes after radiation and T-ALL.
METHODS
Peripheral blood lymphocytes (PBLs) from volunteers and human lymphocyte cell line AHH-1 were irradiated with X-rays to form the chromosome translocations. Phytohemagglutinin (PHA) was used to stimulate lymphocytes. The frequency of translocation was detected by fluorescence in situ hybridization (FISH). Meanwhile, the expression of Ku70 was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot. Furthermore, Ku70 interference, overexpression and chemical inhibition were used in AHH-1 cell lines to confirm the correlation. Finally, the expression of Ku70 in T-ALL samples with or without translocation was detected.
RESULTS
The expression of Ku70 and frequencies of translocation were both significantly increased in PBLs after being irradiated by X-rays, and a positive correlation between the expression (both mRNA and protein level) of Ku70 and the frequency of translocation was detected (r = 0.4877, P = 0.004; r = 0.3038, P = 0.0358 respectively). Moreover, Ku70 interference decreased the frequency of translocations, while the frequency of translocations was not significantly affected after Ku70 overexpression. The expression of Ku70 and frequencies of translocation were both significantly increased in cells after irradiation, combined with chemical inhibition (P < 0.01). The protein level and mRNA level of Ku70 in T-ALL with translocation were obviously higher than T-ALL with normal karyotype (P = 0.009, P = 0.049 respectively).
CONCLUSIONS
Ku70 is closely associated with the frequency of chromosome translocation in human lymphocytes after radiation and T-ALL. Ku70 might be a radiation damage biomarker and a potential tumor therapy target.
Topics: Humans; In Situ Hybridization, Fluorescence; Lymphocytes; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; RNA, Messenger; T-Lymphocytes; Translocation, Genetic
PubMed: 35986335
DOI: 10.1186/s13014-022-02113-3 -
Frontiers in Immunology 2022Thermal injury induces concurrent inflammatory and immune dysfunction, which is associated with adverse clinical outcomes. However, these effects in the pediatric... (Observational Study)
Observational Study
Thermal injury induces concurrent inflammatory and immune dysfunction, which is associated with adverse clinical outcomes. However, these effects in the pediatric population are less studied and there is no standard method to identify those at risk for developing infections. Our goal was to better understand immune dysfunction and identify soluble protein markers following pediatric thermal injury. Further we wanted to determine which early inflammatory, soluble, or immune function markers are most predictive of the development of nosocomial infections (NI) after burn injury. We performed a prospective observational study at a single American Burn Association-verified Pediatric Burn Center. A total of 94 pediatric burn subjects were enrolled and twenty-three of those subjects developed a NI with a median time to diagnosis of 8 days. Whole blood samples, collected within the first 72 hours after injury, were used to compare various markers of inflammation, immune function, and soluble proteins between those who recovered without developing an infection and those who developed a NI after burn injury. Within the first three days of burn injury, innate and adaptive immune function markers (ex vivo lipopolysaccharide-induced tumor necrosis factor alpha production capacity, and ex vivo phytohemagglutinin-induced interleukin-10 production capacity, respectively) were decreased for those subjects who developed a subsequent NI. Further analysis of soluble protein targets associated with these pathways displayed significant increases in soluble CD27, BTLA, and TIM-3 for those who developed a NI. Our findings indicate that suppression of both the innate and adaptive immune function occurs concurrently within the first 72 hours following pediatric thermal injury. At the same time, subjects who developed NI have increased soluble protein biomarkers. Soluble CD27, BTLA, and TIM-3 were highly predictive of the development of subsequent infectious complications. This study identifies early soluble protein makers that are predictive of infection in pediatric burn subjects. These findings should inform future immunomodulatory therapeutic studies.
Topics: Biomarkers; CD27 Ligand; Child; Cross Infection; Hepatitis A Virus Cellular Receptor 2; Humans; Lipopolysaccharides; Phytohemagglutinins; Prospective Studies; Receptors, Immunologic
PubMed: 35958579
DOI: 10.3389/fimmu.2022.940835 -
Cells Aug 2022Pancreatic cancer (PC) remains one of the top 10 causes of cancer-related death in recent years. Approximately 80% of PC patients are diagnosed at the middle or advanced...
Pancreatic cancer (PC) remains one of the top 10 causes of cancer-related death in recent years. Approximately 80% of PC patients are diagnosed at the middle or advanced stage and miss the opportunity for surgery. The demand for early diagnostic methods and reliable biomarkers is increasing, although a number of tumor markers such as CA19-9 and CEA have already been utilized in clinics. In this study, we analyzed the alteration of -glycan of serum glycoproteins by mass spectrometry and lectin blotting. The results showed that bisecting GlcNAc structures of glycoproteins are significantly increased in PC patients' sera. With (PHA-E) lectin that specifically recognizes bisecting GlcNAc -glycans, the serum glycoproteins bearing bisecting GlcNAc in PC patients' sera were pulled down and identified by nano-LC-MS/MS. Among them, ceruloplasmin (Cp) was screened out with a satisfied sensitivity and specificity in identifying PC from acute pancreatitis patients (AUC: 0.757) and normal healthy persons (AUC: 0.972), suggesting a close association between Cp and PC development and diagnosis. To prove that, the Cp expression in tumor tissues of PC patients was examined. The results showed that Cp was significantly upregulated in PC tissues compared to that in adjacent normal tissues. All these results suggested that PHA-E-positive Cp could be a potential PC-specific glycoprotein marker to distinguish PC patients from acute pancreatitis patients and normal persons.
Topics: Acute Disease; CA-19-9 Antigen; Ceruloplasmin; Glycoproteins; Humans; Lectins; Pancreatic Neoplasms; Pancreatitis; Phaseolus; Phytohemagglutinins; Polysaccharides; Tandem Mass Spectrometry
PubMed: 35954297
DOI: 10.3390/cells11152453