scholarly journals A role for the immune system-released activating agent (ISRAA) in the ontogenetic development of brain astrocytes

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0248455
Author(s):  
Aminah M. I. Al-Awadi ◽  
Abdulaziz Isa AlJawder ◽  
Alyaa Mousa ◽  
Safa Taha ◽  
Moiz Bakhiet
Keyword(s):  
Immune System ◽  
Mouse Brain ◽  
Nuclear Translocation ◽  
Age Groups ◽  
Cytokine Network ◽  
Cellular Survival ◽  
Phosphorylated Proteins ◽  
Cell Age ◽  
Activating Agent ◽  
Ifn Γ

The Immune System-Released Activating Agent (ISRAA) was discovered as a novel molecule that functions as a mediator between the nervous and immune systems in response to a nervous stimulus following an immune challenge. This research investigated the role of ISRAA) in promoting the ontogeny of the mouse brain astrocytes. Astrocyte cultures were prepared from two-month-old BALB/c mice. Recombinant ISRAA protein was used to stimulate astrocyte cultures. Immunohistochemistry and ELISA were utilized to measure ISRAA and IFN-γ levels, IFN-γR expression and STAT1 nuclear translocation. MTT-assay was used to evaluate cellular survival and proliferation. To assess astrocyte cell lysates and tyrosine-phosphorylated proteins, SDS-PAGE and western blot were used. ISRAA was highly expressed in mouse embryonic astrocytes, depending on cell age. Astrocytes aged seven days (E7) showed increased proliferation and diminished differentiation, while 21-day-old (E21) astrocytes depicted reversed effects. IFN-γ was involved in the ISRAA action as ISRAA induced IFN-γ in both age groups, but only E21 astrocytes expressed IFN-γR. ISRAA stimulation of E21 resulted in tyrosine phosphorylation of numerous cellular proteins and the nuclear translocation of STAT1, a signalling pathway utilized by IFN-γ. The results suggest that ISRAA is involved in mouse brain development through the cytokine network involving IFN-γ.

scholarly journals A role for the immune system-released activating agent (ISRAA) in the ontogenetic development of brain astrocytes

2021 ◽  
Author(s):  
Aminah M. I. Al-Awadi ◽  
Abdulaziz Isa AlJawder ◽  
Alyaa Mousa ◽  
Safa Taha ◽  
Moiz Bakhiet
Keyword(s):  
Immune System ◽  
Mouse Brain ◽  
Nuclear Translocation ◽  
Age Groups ◽  
Cytokine Network ◽  
Cellular Survival ◽  
Phosphorylated Proteins ◽  
Cell Age ◽  
Activating Agent ◽  
Ifn Γ

AbstractThe Immune System-Released Activating Agent (ISRAA) was discovered as a novel molecule that functions as a mediator between the nervous and immune systems in response to a nervous stimulus following an immune challenge. This research investigated the role of ISRAA) in promoting the ontogeny of the mouse brain astrocytes. Astrocyte cultures were prepared from two-month-old BALB/c mice. Recombinant ISRAA protein was used to stimulate astrocyte cultures. Immunohistochemistry and ELISA were utilized to measure ISRAA and IFN-γ levels, IFN-γR expression and STAT1 nuclear translocation. MTT-assay was used to evaluate cellular survival and proliferation. To assess astrocyte cell lysates and tyrosine-phosphorylated proteins, SDS-PAGE and western blot were used. ISRAA was highly expressed in mouse embryonic astrocytes, depending on cell age. Astrocytes aged seven days (E7) showed increased proliferation and diminished differentiation, while 21-day-old (E21) astrocytes depicted reversed effects. ISRAA stimulated the tyrosine phosphorylation of numerous cellular proteins and the nuclear translocation of STAT1. IFN-γ was involved in the ISRAA action as ISRAA induced IFN-γ in both age groups, but only E21 astrocytes expressed IFN-γR. The results suggest that ISRAA is involved in mouse brain development through the cytokine network involving IFN-γ.

scholarly journals A Critical Role for Immune System-released Activating Agent (Israa) in the Ontogenetic Development of the Brain

2020 ◽  
Author(s):  
Aminah M. I. Al-Awadi ◽  
Abdulaziz Isa AlJawder ◽  
Alyaa Mousa ◽  
Safa Taha ◽  
Moiz Bakhiet
Keyword(s):  
Immune System ◽  
Mouse Brain ◽  
Nuclear Translocation ◽  
Critical Role ◽  
Age Groups ◽  
Cytokine Network ◽  
Cellular Survival ◽  
Phosphorylated Proteins ◽  
Cell Age ◽  
Activating Agent

Abstract Background: The Immune System-Released Activating Agent (ISRAA) was discovered as a novel molecule that functions as a mediator between the nervous and immune systems in response to a nervous stimulus following an immune challenge. Thisresearch investigated the role ofISRAA)in promoting the ontogeny of the mouse brain. Methods: Astrocyte cultures were prepared from two-month-old BALB/c mice. Recombinant ISRAA protein was used to stimulate astrocyte cultures. Immunohistochemistry and ELISA were utilized to measure ISRAA andIFN-g levels, IFN-gR expression and STAT1 nuclear translocation. MTT-assay was used to evaluate cellular survival and proliferation. To assess astrocyte cell lysates and tyrosine-phosphorylated proteins, SDS-PAGE and western blot were used.Results: ISRAA was highly expressed in mouse embryonic astrocytes,depending on cell age. Astrocytes agedseven days (E7) showed increased proliferation and diminisheddifferentiation, while 21-day-old (E21)astrocytes depictedreversed effects. ISRAAstimulated the tyrosine phosphorylation of numerous cellular proteins and thenuclear translocation of STAT1. IFN-g was vital for ISRAAactionas ISRAA induced IFN-gin both age groups, but only E21 astrocytes expressed IFN-gR. Conclusion: The results suggest that ISRAA is cruciallyinvolved in mouse brain development through the cytokine network involving IFN-g.

scholarly journals Sex differences in morphofunctional changes in the immune system in Wistar rats of different age groups with experimental endotoxinemia

2020 ◽  
pp. 65-73
Author(s):  
Anna M. Kosyreva ◽  
Olga V. Makarova
Keyword(s):  
Gender Differences ◽  
Sex Differences ◽  
Immune System ◽  
Peripheral Blood ◽  
Wistar Rats ◽  
Ex Vivo ◽  
Age Groups ◽  
Mature Adult ◽  
Tnf Α ◽  
Ifn Γ

Objective. The aim was revealing gender differences in morphological and functional changes of lymphoid organs (thymus and spleen), changes of cytokine production and subpopulation composition of peripheral blood lymphocytes in Wistar rats of three age groups with endotoxemia. Materials and methods. We used male and female Wistar rats of three age groups: newborns, prepubertal and sexually mature adult rats. A day after the injection of 15 mg/kg of O26:B6 E. coli lipopolysaccharide (LPS), the volume fraction of the functional zones of the thymus and spleen, the number of AnnexinV + apoptotically dying cells in the thymus, the relative and absolute number of lymphocyte subpopulations (CD3+CD4+, CD3+CD8a+, CD4+CD25+Foxp3+, CD3-CD45R+) in peripheral blood and ex vivo production of IL-2, IL-4, IFN-γ and TNF-α were estimated. Results. Sex differences in the response of the immune system after the LPS injection in different age periods are expressed differently: in the neonatal period, there is immunosuppression in females (decrease in the ex vivo production of IL-2, TNF-α and IFN-γ), and there is activation of pro-inflammatory reactions in males (increase in ex vivo production of IL-2 and TNF-α). As compared with other age periods at prepubertal age, LPS-induced immunological disorders are more pronounced, and gender differences are minimal and related only to the number of T-regulatory and B-lymphocytes. In the adults, the LPS-induced immunosuppression is most pronounced in males - they have a decrease in the production of all the cytokines studied and a decrease in the number of cytotoxic and regulatory T-lymphocytes and B-cells. Conclusion. Thus, in each of the studied age periods - newborn, prepubertal and adult, the sexual differences in the immune system reactions are expressed differently and, apparently, these differences are determined by the content of sex steroid hormones, the concentration of which varies with age.

Efficacy of one-dose intramuscular rabies vaccine as pre-exposure prophylaxis in travellers

2021 ◽  
Author(s):  
Deborah J Mills ◽  
Colleen L Lau ◽  
Christine Mills ◽  
Luis Furuya-Kanamori
Keyword(s):  
Immune System ◽  
Rapid Development ◽  
Age Groups ◽  
Rabies Vaccine ◽  
Post Exposure Prophylaxis ◽  
Post Intervention ◽  
Quasi Experimental ◽  
Alternative Schedule ◽  
Insufficient Time ◽  
Exposure Prophylaxis

Abstract Background Current guidelines for rabies pre-exposure prophylaxis (PrEP) recommend multiple vaccine doses. Travellers sometimes present for pre-travel consultation with insufficient time to complete standard PrEP schedules. We investigated the efficacy of one-dose intramuscular (IM) vaccine in priming the immune system (as PrEP) by measuring antibody response to simulated post-exposure prophylaxis (PEP). Methods A quasi-experimental pre–post intervention clinical trial was conducted at a specialist travel clinic in Australia. Adults (≥18 years) without a history of rabies vaccination were included. At Visit 1, seronegative status was confirmed and one dose of 0.5 ml IM rabies vaccine (Verorab®) administered. At Visit 2 (≥60 days after Visit 1), serology was repeated and a simulated PEP dose (0.5 ml IM) given on this day and again 3 days later (Visit 3). Serology was repeated at Visit 4 (7 days after Visit 2). Results A total of 94 antibody-negative participants were included (<50 years [n = 50]; ≥50 years [n = 44]). At Visit 2, 38.0 and 31.8% of participants aged <50 and ≥50 years were antibody-positive (≥0.5 EU/ml). At Visit 4, all participants were antibody-positive; 82.0 and 47.7% of participants aged <50 and ≥50 years had antibody levels >4 EU/ml, respectively. Conclusions One-dose IM vaccine was effective as PrEP for priming the immune system in both age groups, resulting in rapid development of antibodies 7 days after commencing simulated PEP. If there is insufficient time to complete a standard PrEP schedule, one-dose IM could be considered as an alternative schedule for short trips, rather than not offering travellers any doses at all. Clinical trials registration: ACTRN12619000946112.

scholarly journals Effects of age on immune function in broiler chickens

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Bochen Song ◽  
Dazhi Tang ◽  
Shaojia Yan ◽  
Hao Fan ◽  
Guang Li ◽  
...  
Keyword(s):  
Immune System ◽  
Immune Function ◽  
Cellular Immunity ◽  
Mucosal Immunity ◽  
Peripheral Blood ◽  
Broiler Chickens ◽  
Mrna Levels ◽  
Cell Ratio ◽  
Cell Functions ◽  
Ifn Γ

Abstract Background There are many diseases in poultry, many of which are caused by poor immune function. It is not clear how cytokines and various immune cell functions change with age in modern broilers. The purpose of this study was to explore the patterns of development of the immunity of the broiler chickens in cage. Results The results showed that there were 3 development patterns of immunity in the broiler chickens. The first pattern was Down-Up. Cytokines and some immune indicators first decreased and then increased, and the lowest levels of immunity basically occurred from d 6 to 13. The second pattern was Up-Down, and from d 30 to 34, the highest levels of non-specific cellular immunity components, such as the peripheral blood mononuclear macrophage ratio, specific cellular immunity components, such as the peripheral blood helper T (Th) cell ratio and T cell and B cell proliferation activity, and mucosal immunity components, such as the ileal CD4, TGF-β1 and IgA mRNA levels, were observed. The third pattern was Up-Up, and the levels of the non-specific cellular immunity components, such as the serum nitric oxide (NO), C3 and C4 levels, the specific cellular immunity components, such as the spleen index, peripheral blood IL-2, IFN-γ/IL-4, cytotoxic T (Tc) cell ratio, and splenic NF-κB mRNA levels, the humoral immunity components, such as the serum IgG level, the mucosal immunity components, such as the ileal MHC-II, CD3d, TCRβ subunit, TCRζ subunit, IFN-γ, pIgR mRNA and ileal mucosa sIgA levels, were continuing to increase from d 1 to 34. Conclusions It could be concluded that the immune system and its function have not developed well in the broiler chickens d 6 to 13 and that the immune system does not mature until d 30 to 34 in the broiler chickens in cages. It is necessary to enhance the immune function of the broiler chickens through nutritional measures from d 1 to 30.

The Effect of Exercise and Psychological Stress on Anti- and Proinflammatory Cytokines

2021 ◽  
pp. 1-8
Author(s):  
Sara Hasanli ◽  
Sarah Hojjati ◽  
Maryam Koushkie Jahromi
Keyword(s):  
Immune System ◽  
Synergistic Effect ◽  
Psychological Stress ◽  
Proinflammatory Cytokines ◽  
Research Evidence ◽  
Study Groups ◽  
Acute Response ◽  
Exercise Activity ◽  
Ifn Γ ◽  
Control Exercise

<b><i>Background/Aims:</i></b> Research evidence regarding immune system responses and adaptations to psychological or physical stresses is controversial. This study aimed to investigate the effect of 8-week psychological stress and exercise activity (chronic adaptation) and the acute response of possibly adapted rats to psychological stress and exercise considering IFN-γ, IL-4, and IL-4/IFN-γ. <b><i>Methods:</i></b> Thirty-two rats were divided into 4 groups of 8 animals including control, exercise, psychological stress, and combination of exercise with psychological stress. IL-4 and IFN-γ cytokines were measured pre-experiment (preEX), immediately postexercise (IpostEX), and 72-h postexperiment protocol (72hpostEX). <b><i>Results:</i></b> There were no significant differences between the study groups regarding IFN-γ, IL-4, and IL-4/IFN-γ in preEX (<i>p</i> &#x3e; 0.05), IpostEX (<i>p</i> &#x3e; 0.05), and 72hpostEX (<i>p</i> &#x3e; 0.05). However, IL-4 increased significantly in IpostEX compared with preEX in exercise (<i>p</i> = 0.012) and combination of exercise with psychological stress (<i>p</i> = 0.03) groups. <b><i>Conclusions:</i></b> Exercise and combination of exercise and psychological stress induce similar acute response to IL-4 in chronic trained and stressed rats. Also, exercise may induce an acute synergistic effect with psychological stress on IL-4.

scholarly journals Gomisin M2 Ameliorates Atopic Dermatitis-like Skin Lesions via Inhibition of STAT1 and NF-κB Activation in 2,4-Dinitrochlorobenzene/Dermatophagoides farinae Extract-Induced BALB/c Mice

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4409
Author(s):  
Jinjoo Kang ◽  
Soyoung Lee ◽  
Namkyung Kim ◽  
Hima Dhakal ◽  
Taeg-Kyu Kwon ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Oral Administration ◽  
Skin Diseases ◽  
Nuclear Translocation ◽  
Skin Lesions ◽  
Biologically Active ◽  
Therapeutic Effects ◽  
Dermatophagoides Farinae ◽  
Tnf Α ◽  
Ifn Γ

The extracts of Schisandra chinensis (Turcz.) Baill. (Schisandraceae) have various therapeutic effects, including inflammation and allergy. In this study, gomisin M2 (GM2) was isolated from S. chinensis and its beneficial effects were assessed against atopic dermatitis (AD). We evaluated the therapeutic effects of GM2 on 2,4-dinitrochlorobenzene (DNCB) and Dermatophagoides farinae extract (DFE)-induced AD-like skin lesions with BALB/c mice ears and within the tumor necrosis factor (TNF)-α and interferon (IFN)-γ-stimulated keratinocytes. The oral administration of GM2 resulted in reduced epidermal and dermal thickness, infiltration of tissue eosinophils, mast cells, and helper T cells in AD-like lesions. GM2 suppressed the expression of IL-1β, IL-4, IL-5, IL-6, IL-12a, and TSLP in ear tissue and the expression of IFN-γ, IL-4, and IL-17A in auricular lymph nodes. GM2 also inhibited STAT1 and NF-κB phosphorylation in DNCB/DFE-induced AD-like lesions. The oral administration of GM2 reduced levels of IgE (DFE-specific and total) and IgG2a in the mice sera, as well as protein levels of IL-4, IL-6, and TSLP in ear tissues. In TNF-α/IFN-γ-stimulated keratinocytes, GM2 significantly inhibited IL-1β, IL-6, CXCL8, and CCL22 through the suppression of STAT1 phosphorylation and the nuclear translocation of NF-κB. Taken together, these results indicate that GM2 is a biologically active compound that exhibits inhibitory effects on skin inflammation and suggests that GM2 might serve as a remedy in inflammatory skin diseases, specifically on AD.

Tyrosine kinase inhibitors and antioxidants modulate NF-κB and NOS-II induction in retinal epithelial cells

1998 ◽  
Vol 275 (1) ◽  
pp. C208-C215 ◽  
Author(s):  
Violaine Faure ◽  
Yves Courtois ◽  
Olivier Goureau
Keyword(s):  
Epithelial Cells ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Intracellular Signaling ◽  
Kinase Inhibitors ◽  
Nuclear Translocation ◽  
Pyrrolidine Dithiocarbamate ◽  
Dependent Manner ◽  
Mrna Accumulation ◽  
Ifn Γ

Bovine retinal pigmented epithelial (RPE) cells express an inducible nitric oxide synthase (NOS-II) after activation with interferon-γ (IFN-γ) and lipopolysaccharide (LPS). Experiments were performed to investigate the effects of tyrosine kinase inhibitors (genistein and herbimycin A) and antioxidants [pyrrolidine dithiocarbamate (PDTC) and butyl hydroxyanisol] on NOS-II induction. The LPS-IFN-γ-induced nitrite release was inhibited in a concentration-dependent manner by these compounds. Analysis by Northern blot showed that this inhibitory effect correlated with a decrease in NOS-II mRNA accumulation. Analysis by electrophoretic mobility shift assay of the activation of the transcription factor nuclear factor-κB (NF-κB) involved in NOS-II induction demonstrated that LPS alone or combined with IFN-γ induced NF-κB binding. NF-κB activation was not changed by the presence of tyrosine kinase inhibitors but was totally prevented by PDTC pretreatment. Immunocytochemistry experiments confirmed the reduction of the nuclear translocation of NF-κB only by PDTC. Our results demonstrated the existence in retinal pigmented epithelial cells of different intracellular signaling pathways in NOS-II induction, since tyrosine kinase inhibitors blocked NOS-II mRNA accumulation without inhibiting NF-κB activation. Furthermore, the LPS-IFN-γ-induced NOS-II mRNA accumulation was sensitive to cycloheximide, suggesting that, in addition to NF-κB, transcriptional factors that require new protein synthesis are involved in NOS-II induction.

scholarly journals The Linker Domain of Stat1 Is Required for Gamma Interferon-Driven Transcription

1999 ◽  
Vol 19 (7) ◽  
pp. 5106-5112 ◽  
Author(s):  
Edward Yang ◽  
Zilong Wen ◽  
Richard L. Haspel ◽  
Jue J. Zhang ◽  
James E. Darnell
Keyword(s):  
Dna Binding ◽  
Nuclear Translocation ◽  
Contact Point ◽  
Sh2 Domain ◽  
Gamma Interferon ◽  
Transactivation Domain ◽  
Dimerization Domain ◽  
Transcriptional Responses ◽  
Ifn Γ ◽  
Linker Domain

ABSTRACT Upon binding of gamma interferon (IFN-γ) to its receptor, the latent transcription factor Stat1 becomes phosphorylated, dimerizes, and enters the nucleus to activate transcription. In response to IFN-α, Stat1 binds to Stat2 in a heterodimer that recruits p48, an IRF family member, to activate transcription. A number of functional domains of the STATs, including a C-terminal transactivation domain, a dimerization domain, and an SH2 domain, are known. However, the highly conserved residues between the DNA binding and SH2 domains (463 to 566), recently christened the linker domain on the basis of crystallographic studies, have remained without a known function. In the present study, we report that KE544-545AA point mutants in Stat1 abolish transcriptional responses to IFN-γ but not to IFN-α. We further show that this mutant Stat1 undergoes normal phosphorylation, nuclear translocation, and DNA binding. Taken together with recent structural evidence, these results suggest that the linker domain acts as a critical contact point during the construction of a Stat1-driven transcriptional complex.

scholarly journals EGF receptor–mediated FUS phosphorylation promotes its nuclear translocation and fibrotic signaling

2020 ◽  
Vol 219 (9) ◽  
Author(s):  
Manuel Chiusa ◽  
Wen Hu ◽  
Jozef Zienkiewicz ◽  
Xiwu Chen ◽  
Ming-Zhi Zhang ◽  
...  
Keyword(s):  
Egf Receptor ◽  
Nuclear Translocation ◽  
Collagen Iv ◽  
Phosphorylation Sites ◽  
Kidney Fibrosis ◽  
Antifibrotic Therapy ◽  
Phosphorylated Proteins ◽  
Fused In Sarcoma ◽  
A Cell ◽  
Excessive Accumulation

Excessive accumulation of collagen leads to fibrosis. Integrin α1β1 (Itgα1β1) prevents kidney fibrosis by reducing collagen production through inhibition of the EGF receptor (EGFR) that phosphorylates cytoplasmic and nuclear proteins. To elucidate how the Itgα1β1/EGFR axis controls collagen synthesis, we analyzed the levels of nuclear tyrosine phosphorylated proteins in WT and Itgα1-null kidney cells. We show that the phosphorylation of the RNA-DNA binding protein fused in sarcoma (FUS) is higher in Itgα1-null cells. FUS contains EGFR-targeted phosphorylation sites and, in Itgα1-null cells, activated EGFR promotes FUS phosphorylation and nuclear translocation. Nuclear FUS binds to the collagen IV promoter, commencing gene transcription that is reduced by inhibiting EGFR, down-regulating FUS, or expressing FUS mutated in the EGFR-targeted phosphorylation sites. Finally, a cell-penetrating peptide that inhibits FUS nuclear translocation reduces FUS nuclear content and collagen IV transcription. Thus, EGFR-mediated FUS phosphorylation regulates FUS nuclear translocation and transcription of a major profibrotic collagen gene. Targeting FUS nuclear translocation offers a new antifibrotic therapy.

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