Upregulation of Interferon-stimulated Genes and Interleukin-10 in Peripheral Blood Immune Cells During Early Pregnancy in Dairy Cows

Abstract Circulating prostaglandin F2α metabolite (PGFM) after an oxytocin challenge was evaluated throughout the first 2 months of pregnancy in lactating Holstein cows. On day 11, 18, and 25 after artificial insemination (AI), and on days 32, 39, 46, 53, and 60 of pregnancy, cows were challenged with 50 IU oxytocin, i.m. Blood was collected before (0 min), 30, 60, 90, and 120 min after oxytocin for plasma PGFM concentrations. Ultrasound evaluations were performed for pregnancy diagnosis on day 32–60 post-AI. Nonpregnant (NP) cows on day 18 were designated by a lack of interferon-stimulated genes in peripheral blood leukocytes and Pregnant (P) based on day 32 ultrasound. On day 11, P and NP were similar with low PGFM and no effect of oxytocin on PGFM. On day 18, oxytocin increased PGFM (3-fold) in NP with little change in P cows. Comparing only P cows from day 11 to 60, basal circulating PGFM increased as pregnancy progressed, with day 11 and 18, lower than all days from day 25 to 60 of pregnancy. Oxytocin-induced PGFM in P cows on day 25 was greater than P cows on day 18 (2.9-fold). However, oxytocin-induced PGFM was lower on day 25 compared to day 53 and 60, with intermediate values on day 32, 39, and 46 of pregnancy. Thus, the corpus luteum (CL) of early pregnancy (day 11, 18) is maintained by suppression of PGF, as reflected by suppressed PGFM in this study. However, during the second month of pregnancy, uterine PGF secretion was not suppressed since basal PGFM and oxytocin-induced PGFM secretion were elevated. Apparently, mechanisms other than suppression of oxytocin receptors maintain CL after day 25 of pregnancy.

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Regulation of Interferon-Stimulated Genes in Peripheral Blood Leukocytes in Pregnant and Bred, Nonpregnant Dairy Cows

Journal of Dairy Science ◽

10.3168/jds.s0022-0302(07)72628-0 ◽

2007 ◽

Vol 90 (1) ◽

pp. 274-280 ◽

Cited By ~ 137

Author(s):

C.A. Gifford ◽

K. Racicot ◽

D.S. Clark ◽

K.J. Austin ◽

T.R. Hansen ◽

...

Keyword(s):

Dairy Cows ◽

Peripheral Blood ◽

Peripheral Blood Leukocytes ◽

Blood Leukocytes ◽

Interferon Stimulated Genes

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Early pregnancy-induced transcripts in peripheral blood immune cells in Bos indicus heifers

Scientific Reports ◽

10.1038/s41598-020-70616-8 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Cecilia Constantino Rocha ◽

Sónia Cristina da Silva Andrade ◽

Gabriela Dalmaso de Melo ◽

Igor Garcia Motta ◽

Luiz Lehmann Coutinho ◽

...

Keyword(s):

Early Pregnancy ◽

Immune Cells ◽

Peripheral Blood ◽

Bos Indicus

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10.11606/d.10.2020.tde-17022020-143809 ◽

2020 ◽

Author(s):

Cecília Constantino Rocha

Keyword(s):

Early Pregnancy ◽

Immune Cells ◽

Peripheral Blood

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XMODULATION IN MICEAND MEN: IL-10 PRODUCING CELLS INBLOOD AND LYMPHOID TISSUE

Clinical & Investigative Medicine ◽

10.25011/cim.v31i4.4789 ◽

2008 ◽

Vol 31 (4) ◽

pp. 3

Author(s):

L Barrett ◽

M Grant ◽

R Liwski ◽

K West

Keyword(s):

Immune System ◽

Peripheral Blood ◽

Lymphoid Tissue ◽

Mononuclear Cells ◽

Ex Vivo ◽

White Blood Cells ◽

Interleukin 10 ◽

Healthy Individuals ◽

Human Immune System ◽

Healthy Humans

Background: The human immune system provides remarkable protection from a plethora of pathogens, but can cause damage when activated for a prolonged time (as inpersistent infections) or against self (autoimmunity). Therefore, mechanisms of immune system downregulation and control are imperative. There is little data on how the immune system is controlled in healthy individuals. We recently described a novel population of white blood cells that constitutively produce the immunomodulatory cytokine interleukin-10 (IL-10). Our objective was to further delineate the distribution of these cells in human and mouse models, as well as potential triggers for interleukin-10 production in vitro. Methods: Human and animal protocols were reviewed and approved by the institutional ethics board and animal care facilities, and informed consent was obtained from all human donors. The ex vivo percentage of peripheral blood CD36^+IL-10^+ mononuclear cells was assessed by intracellular flow cytometry in 10 healthy individuals. IL-10 production after exposure to twoCD36 ligands, thrombospondin and oxidized low density lipoprotein (oxLDL) was measured at 8 hours. Peripheral blood mononuclear cells and splenocytes from BL/6 (n=5) and Balb/c (n=1) micewere assessed for CD36^+IL-10^+ cells ex vivo as well. Results: The percentage of CD36^+IL-10^+ cells in peripheral blood fromhealthy individuals ranges between 0.1% and 0.9%. The percentage was similar in mouse peripheral blood, with a range of 0.4%-1.1%. These cells were also found in mouse spleen at a higher frequency than peripherally (1.1-1.5%). Human CD36^+IL-10^+ cells have more IL-10 when exposed to thrombospondin, oxLDL. Conclusions: Our novel population of IL-10 producing cells is found not only in healthy humans, but also in lymphoid tissue and blood from pathogen free mice. This highlights the evolutionary conservation of the cell across species, and suggests an important homeostatic function. The physiologic ligands for CD36 are ubiquitous in circulation, and ourin vitro data suggests a link between CD36 ligation and IL-10 production. IL-10 is a known immune system modulator, and its production by these cells may help maintain homeostaticcontrol of the immune system.

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The effect of dexamethasone on mucosal immunity of uterine tissue during pregnancy in rat

Mansoura Veterinary Medical Journal ◽

10.35943/mvmj.2019.01.1013 ◽

2019 ◽

Vol 20 (1) ◽

pp. 75-84

Keyword(s):

Early Pregnancy ◽

Histopathological Examination ◽

Early Period ◽

Interleukin 10 ◽

Treated Group ◽

Female Rats ◽

Male Rats ◽

Mrna Levels ◽

Uterine Tissue ◽

Leukocytic Infiltration

Disturbances in early pregnancy immunity affect embryo development, endometrial receptivity, placental development, fetal growth and lead to subfertility, dexamethasone is a synthetic glucocorticoid used for treatment of various complications. Immune cells and cytokines were examined during the early pregnancy in twenty-four female rats and six male rats for mating. Rats were grouped into two group control and dexamethasone treated by a dose of 50µgm/kgm body weight daily starting from one week before mating and persisted for one week after pregnancy. Blood samples were collected from each rat at 5hrs and at 1,3,7 day of pregnancy. Extracted RNA was subjected to real time PCR to determine mRNA levels for immune related genes interleukin1a(IL1A) and interleukin 10(IL10). Histopathological examination was done to uterus in order to detect leukocyte infiltration in uterine tissue. Results showed that significant increase in white blood cell count mainly eosinophil at 5hrs and lymphocyte at three and seven day of pregnancy of dexamethasone treated group. Moreover, TNF, C-reactive protein and progesterone were increased mainly at seven day of pregnancy of dexamethasone treated group. Similarly, interleukin 1alpha and interleukin 10 significantly increased at 5hrs and one day of pregnancy of dexamethasone treated group. In contrast, serum levels of total antioxidant capacity and estrogen were decreased significantly at 5hrs and seven day in dexamethasone treated group. Histopathological examination of uterus revealed leukocytic infiltration especially neutrophil and few eosinophils at five hours and one day of gestation then eosinophil become absent at 3day and seven day of dexamethasone group. Epithelial height and uterine gland diameter significantly increased at 5hrs, three day and seven days of gestation of dexamethasone treated group. The present investigation demonstrated that using of dexamethasone by dose of 50µgm/kgm during early pregnancy had a conflicting impact on some immune cytokines and parameters and may reflect a harmful response of immune system toward early period of pregnancy

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OP0054 NEW ROLE FOR PROTEINASE 3 IN IL-16 BIOACTIVITY CONTROL IN GRANULOMATOSIS WITH POLYANGIITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.1314 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 28.1-29

Author(s):

A. Kerstein-Staehle ◽

C. Alarcin ◽

J. Luo ◽

G. Riemekasten ◽

P. Lamprecht ◽

...

Keyword(s):

Cell Death ◽

Western Blot ◽

Disease Activity ◽

Chronic Inflammation ◽

Immune Cells ◽

Peripheral Blood ◽

Granulomatosis With Polyangiitis ◽

Granulomatous Inflammation ◽

Proteinase 3 ◽

Sds Page

Background:The immunomodulatory cytokine IL-16 is increased in several inflammatory and autoimmune diseases1. IL-16 recruits and activates CD4+ immune cells such as T cells, dendritic cells, or monocytes. IL-16 is produced by various immune and non-immune cells, but synthesis and storage of IL-16 is regulated differentially depending on the cell type and stimulation. For its biological activity, IL-16 cleavage by caspase-3 is required1. Necrotizing granulomatous inflammation is a hallmark of granulomatosis with polyangiitis (GPA) with neutrophil dysregulation as a central driver of chronic inflammation and autoimmunity2. Earlier studies showed a correlation between increased serum IL-16 and disease parameters in AAV, including GPA3, but functional evidence for a direct link between IL-16 and neutrophils in granulomatous inflammation is missing so far.Objectives:In this study we aim to identify a functional link between increased IL-16, neutrophils, and the autoantigen proteinase 3 (PR3) with regard to chronic inflammation and autoimmunity in GPA.Methods:IL-16 was measured in sera of GPA patients (n = 40) and healthy controls (HC, n = 50) by ELISA and correlated with clinical features, such as disease activity (BVAS), creatinine, GFR, VDI and PR3-ANCA status. IL-16 protein expression was analyzed in peripheral blood mononuclear cells (PBMC) and polymorphonuclear cells (PMN) from GPA patients and HC (n = 5, each) by SDS-PAGE and western blot. Binding affinity of recombinant pro-IL-16 to native human PR3 was assessed by microscale thermophoresis. Cleavage of pro-IL-16 by active human PR3 was performed at various time points at 37°C. Cleavage products were analyzed by SDS-PAGE and western blot.Results:Circulating IL-16 was significantly increased in GPA patients compared to HC. Elevated IL-16 positively correlated with BVAS, creatinine, VDI and PR3-ANCA status and negatively correlated with GFR. In PMBC and PMN from GPA and HC we identified different expression patters of precursor and active forms of IL-16. In healthy PBMC we found high amounts of precursor (80kD), pro-IL-16 (55kD) and active IL-16 (17kD). In contrast, PBMC from GPA patients had lower amounts of pro-IL-16 and no active IL-16, indicating activation and secretion of IL-16 due to inflammatory stimulation, as shown earlier5. In GPA PMN we detected no precursor IL-16, but pro-IL-16 and its active form, in contrast to very low amounts of all IL-16 forms in healthy PMN. Processing and release of IL-16 in neutrophils has been linked to apoptosis and secondary necrosis5. By interaction studies we demonstrated direct binding of pro-IL-16 to PR3 with a Kd of 10 nM. In a subsequent cleavage assay we confirmed IL-16 processing by PR3 in a time-dependent manner.Conclusion:Correlation of serum IL-16 with clinical features of GPA suggests that IL-16 is associated with markers of disease activity, tissue damage and autoreactivity. We showed that PBMC and PMN represent a source of IL-16 in GPA. By the identification of PR3 as an additional IL-16-activating enzyme we could demonstrate a potential link between excessive PR3 expression, cell death and IL-16-dependent mechanisms, contributing to chronic granulomatous inflammation and autoimmunity in GPA.References:[1]Glass, W. G. et al. Not-so-sweet sixteen: The role of IL-16 in infectious and immune-mediated inflammatory diseases. J. Interf. Cytokine Res. 26, 511–520 (2006).[2]Millet, A. et al. Proteinase 3 on apoptotic cells disrupts immune silencing in autoimmune vasculitis. J. Clin. Invest. 125, 4107–4121 (2015).[3]Yoon, T. et al. Serum interleukin-16 significantly correlates with the Vasculitis Damage Index in antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Res. Ther. 22, 1–6 (2020).[4]Elssner, A. et al. IL-16 Is Constitutively Present in Peripheral Blood Monocytes and Spontaneously Released During Apoptosis. J. Immunol. 172, 7721–7725 (2004).[5]Roth, S. et al. Secondary necrotic neutrophils release interleukin-16C and macrophage migration inhibitory factor from stores in the cytosol. Cell Death Discov. 1, 15056 (2015).Disclosure of Interests:None declared

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Peripheral Blood Biomarkers CXCL12 and TNFRSF13C Associate with Cerebrospinal Fluid Biomarkers and Infiltrating Immune Cells in Alzheimer Disease

Journal of Molecular Neuroscience ◽

10.1007/s12031-021-01809-7 ◽

2021 ◽

Author(s):

Qianqian Wu ◽

Wei Kong ◽

Shuaiqun Wang

Keyword(s):

Cerebrospinal Fluid ◽

Alzheimer Disease ◽

Immune Cells ◽

Peripheral Blood ◽

Blood Biomarkers ◽

Cerebrospinal Fluid Biomarkers

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Recent Possibilities for the Diagnosis of Early Pregnancy and Embryonic Mortality in Dairy Cows

Animals ◽

10.3390/ani11061666 ◽

2021 ◽

Vol 11 (6) ◽

pp. 1666

Author(s):

Ottó Szenci

Keyword(s):

Blood Flow ◽

Dairy Cows ◽

Early Pregnancy ◽

Fetal Mortality ◽

Reproductive Efficiency ◽

Interferon Tau ◽

Early Pregnancy Factor ◽

Pelvic Inlet ◽

On Farm ◽

Protein Assays

One of the most recent techniques for the on-farm diagnosis of early pregnancy (EP) in cattle is B-mode ultrasonography. Under field conditions, acceptable results may be achieved with ultrasonography from Days 25 to 30 post-AI. The reliability of the test greatly depends on the frequency of the transducer used, the skill of the examiner, the criterion used for a positive pregnancy diagnosis (PD), and the position of the uterus in the pelvic inlet. Non-pregnant animals can be selected accurately by evaluating blood flow in the corpus luteum around Day 20 after AI, meaning we can substantially improve the reproductive efficiency of our herd. Pregnancy protein assays (PSPB, PAG-1, and PSP60 RIA, commercial ELISA or rapid visual ELISA tests) may provide an alternative method to ultrasonography for determining early pregnancy or late embryonic/early fetal mortality (LEM/EFM) in dairy cows. Although the early pregnancy factor is the earliest specific indicator of fertilization, at present, its detection is entirely dependent on the use of the rosette inhibition test; therefore, its use in the field needs further developments. Recently found biomarkers like interferon-tau stimulated genes or microRNAs may help us diagnose early pregnancy in dairy cows; however, these tests need further developments before their general use in the farms becomes possible.

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