scholarly journals Repeated stimulation of the HPA axis alters white blood cell count without increasing oxidative stress or inflammatory cytokines in fasting elephant seal pups

2021 ◽  
Vol 224 (18) ◽  
Author(s):  
David C. Ensminger ◽  
Daniel E. Crocker ◽  
Emily K. Lam ◽  
Kaitlin N. Allen ◽  
José Pablo Vázquez-Medina
Keyword(s):  
Oxidative Stress ◽  
Hpa Axis ◽  
Blood Cells ◽  
Transforming Growth Factor ◽  
White Blood Cells ◽  
Elevated Serum ◽  
Transforming Growth Factor Β ◽  
Elephant Seal ◽  
Serum Aldosterone ◽  
Antagonist Ru486

ABSTRACT The hypothalamic–pituitary–adrenal (HPA) axis controls the release of glucocorticoids, which regulate immune and inflammatory function by modulating cytokines, white blood cells and oxidative stress via glucocorticoid receptor (GR) signaling. Although the response to HPA activation is well characterized in many species, little is known about the impacts of HPA activation during extreme physiological conditions. Hence, we challenged 18 simultaneously fasting and developing elephant seal pups with daily intramuscular injections of adrenocorticotropin (ACTH), a GR antagonist (RU486), or a combination of the two (ACTH+RU486) for 4 days. We collected blood at baseline, 2 h and 4 days after the beginning of treatment. ACTH and ACTH+RU486 elevated serum aldosterone and cortisol at 2 h, with effects diminishing at 4 days. RU486 alone induced a compensatory increase in aldosterone, but not cortisol, at 4 days. ACTH decreased neutrophils at 2 h, while decreasing lymphocytes and increasing the neutrophil:lymphocyte ratio at 4 days. These effects were abolished by RU486. Despite alterations in white blood cells, there was no effect of ACTH or RU486 on transforming growth factor-β or interleukin-6 levels; however, both cytokines decreased with the 4 day fasting progression. Similarly, ACTH did not impact protein oxidation, lipid peroxidation or antioxidant enzymes, but plasma isoprostanes and catalase activity decreased while glutathione peroxidase increased with fasting progression. These data demonstrate differential acute (2 h) and chronic (4 days) modulatory effects of HPA activation on white blood cells and that the chronic effect is mediated, at least in part, by GR. These results also underscore elephant seals' extraordinary resistance to oxidative stress derived from repeated HPA activation.

scholarly journals Repeated stimulation of the HPA axis alters white blood cell counts without increasing oxidative stress or inflammatory cytokines in fasting elephant seal pups

2021 ◽  
Author(s):  
David C Ensminger ◽  
Daniel E Crocker ◽  
Emily K Lam ◽  
Kaitlin N Allen ◽  
Jose Pablo Vazquez-Medina
Keyword(s):  
Oxidative Stress ◽  
Hpa Axis ◽  
Marine Mammals ◽  
Transforming Growth Factor ◽  
White Blood Cells ◽  
Elevated Serum ◽  
Transforming Growth Factor Β ◽  
Elephant Seal ◽  
Cell Counts ◽  
White Blood Cell Counts

The hypothalamic-pituitary-adrenal (HPA) axis controls the release of glucocorticoids, which regulate immune and inflammatory function by modulating cytokines, white blood cells (WBCs), and oxidative stress via glucocorticoid receptor (GR) signaling. Although the response to HPA activation is well characterized in many species, little is known about the impacts of HPA activation during extreme physiological conditions in marine mammals. Hence, we challenged 18 simultaneously fasting and developing elephant seal pups with daily intramuscular injections of adrenocorticotropin (ACTH), a GR antagonist (RU486), or a combination (ACTH+RU486) for four days (4d). We collected blood at baseline, two hours (2h), and 4d after the beginning of treatment. ACTH and ACTH+RU486 elevated serum aldosterone and cortisol at 2h, with effects diminishing at 4d. RU486 alone induced a compensatory increase in aldosterone, but not cortisol, at 4d. ACTH decreased neutrophils at 2h while decreasing lymphocytes and increasing neutrophil:lymphocyte ratio at 4d. These effects were abolished by RU486. Despite alterations in WBCs, there was no effect of ACTH or RU486 on transforming growth factor-β or interleukin-6 levels; however, both cytokines decreased with the 4-d fasting progression. Similarly, ACTH did not impact protein oxidation, lipid peroxidation, or antioxidant enzymes, but plasma isoprostanes and catalase activity decreased while glutathione peroxidase increased with fasting progression. These data demonstrate differential acute (2h) and chronic (4d) modulatory effects of HPA activation on WBCs and that the chronic effect is mediated, at least in part, by GR. These results also underscore elephant seals' resistance to potential oxidative stress derived from repeated HPA activation.

scholarly journals Transforming growth factor-β released by apoptotic white blood cells during red blood cell storage promotes transfusion-induced alloimmunomodulation

Transfusion ◽  
2015 ◽  
Vol 55 (7) ◽  
pp. 1721-1735 ◽  
Author(s):  
Romain Vallion ◽  
Francis Bonnefoy ◽  
Anna Daoui ◽  
Loredane Vieille ◽  
Pierre Tiberghien ◽  
...  
Keyword(s):  
Growth Factor ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Blood Cells ◽  
Transforming Growth Factor ◽  
White Blood Cells ◽  
Transforming Growth Factor Β ◽  
Cell Storage

scholarly journals Elevated Serum Transforming Growth Factor β1 Levels in Epstein-Barr Virus-Associated Diseases and Their Correlation with Virus-Specific Immunoglobulin A (IgA) and IgM

2000 ◽  
Vol 74 (5) ◽  
pp. 2443-2446 ◽  
Author(s):  
Jingwu Xu ◽  
Ali Ahmad ◽  
James F. Jones ◽  
Riccardo Dolcetti ◽  
Emanuela Vaccher ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epstein Barr Virus ◽  
Transforming Growth Factor ◽  
Immunoglobulin A ◽  
Elevated Serum ◽  
Transforming Growth Factor Β ◽  
Serum Levels ◽  
Barr Virus ◽  
Associated Diseases ◽  
Epstein Barr

ABSTRACT Transforming growth factor β (TGF-β) is an immunosuppressive cytokine which can induce immunoglobulin A (IgA) switch and Epstein-Barr virus (EBV) replication in latently infected cells. Here we report elevated serum levels of TGF-β in various EBV-associated diseases correlating positively with EBV-specific IgA titers and negatively with IgM titers, suggesting a role for this cytokine in the pathogenesis of these diseases.

scholarly journals Serological level of transforming growth factor-β as a predictive biomarker of aortic enlargement in patients with Marfan syndrome

2017 ◽  
Vol 8 (1) ◽  
pp. 61-66
Author(s):  
Andrey S Rudoy ◽  
Alexey M Uryvaev
Keyword(s):  
Risk Factors ◽  
Growth Factor ◽  
Marfan Syndrome ◽  
Aortic Root ◽  
Transforming Growth Factor ◽  
Aortic Rupture ◽  
Imaging Techniques ◽  
Elevated Serum ◽  
Transforming Growth Factor Β ◽  
Absolute Size

Marfan syndrome - an inherited, autosomal dominant disease with an expected rate of 3-5/10 000 or fraction of 20-25% of new mutations, accompanied by violation of the connective tissue that occurs as a result of gene mutations FBN1, coding for the synthesis of fibrillin-1, performing the most important role in the modulation physiological bioavailability TGF-β (transforming growth factor-β). Prediction of aortic rupture is based on the identification of risk factors: family history, the absolute size of the aortic root, the rate of expansion of the aorta, which are based on the results of the history and techniques of imaging ultrasound, CT, MRI. At the same time there is a chance of developing aortic rupture under normal aortic root size and the absence of any risk factors, as well as after the prophylactic prosthetic aortic root. This makes it necessary to search for alternative prognostic markers, threatening bundle and rupture of the aorta. Article verified the predictive role of TGF-β as a serological biomarker for assessing the extension of the aortic root in patients with Marfan syndrome (n = 23, F : M / 7 : 16; 33 ± 9.3 years). The article describes the patterns between TGF-β and the size and the reconstruction of the aneurysm of the thoracic aorta. It was found that elevated levels of serum TGF-β1 (49.1 ng/ml Vs 29.15 ng/ml in the control, p < 0.05) in patients with MS diagnosed with an extension of the aortic root (Z > 1.96) can serve as a serological marker to poor prognosis, accompanied by an increase in the size of the aortic root. In patients with normal-sized aorta, and after aortic reconstruction serum TGFβ1 not elevated. Serum TGFβ may be a promising target for therapeutic, diagnostic and prognostic tactics which are not based on imaging techniques.

scholarly journals Effect of aspartame on biochemical and oxidative stress parameters in rat blood

2015 ◽  
Vol 67 (2) ◽  
pp. 535-545 ◽  
Author(s):  
Marko Prokic ◽  
Milica Paunovic ◽  
Milos Matic ◽  
Natasa Djordjevic ◽  
Branka Ognjanovic ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Biochemical Parameters ◽  
White Blood Cells ◽  
Lipid Peroxides ◽  
Hdl Cholesterol ◽  
Albino Rats ◽  
Total Body Mass ◽  
Antioxidative Status

Aspartame (ASP) is one of the most widely used nonnutritive sweeteners. This study investigates the chronic effects of ASP on hematological and biochemical parameters, and its effects on the oxidative/antioxidative status in the red blood cells of Wistar albino rats. Rats were provided with ASP (40 mg/kg/daily for six weeks) in drinking water. Increased food and fluid intake was observed in the ASP-treated rats. Total body mass was significantly decreased in the ASP-treated rats. Treatment with ASP caused an increase in the concentrations of glucose, cholesterol, LDL-cholesterol, and in the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH), as well as a decrease in the levels of HDL-cholesterol in the serum. A significant decline in the number of white blood cells (WBC) was observed after ASP uptake. Based on the results we conclude that ASP induces oxidative stress, observed as an alteration of the glutathione redox status, which leads to increased concentrations of nitric oxide (NO) and lipid peroxides (LPO) in the red blood cells. Changes in biochemical parameters, lipid metabolism, as well as changes in the levels of oxidative stress markers and the appearance of signs of liver damage indicate that chronic use of ASP can lead to the development of hyperglycemia, hypercholesterolemia and associated diseases.

scholarly journals The expression of transforming growth factor β in pregnant rat myometrium is hormone and stretch dependent

Reproduction ◽  
2007 ◽  
Vol 134 (3) ◽  
pp. 503-511 ◽  
Author(s):  
Oksana Shynlova ◽  
Prudence Tsui ◽  
Anna Dorogin ◽  
B Lowell Langille ◽  
Stephen J Lye
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Late Gestation ◽  
Quiescent State ◽  
Mrna Levels ◽  
Pregnant Rats ◽  
Pregnant Rat ◽  
Threefold Increase ◽  
Antagonist Ru486

From a quiescent state in early pregnancy to a highly contractile state in labor, the myometrium displays tremendous growth and remodeling. We hypothesize that the transforming growth factor β (TGFβ) system is involved in the differentiation of pregnant myometrium throughout gestation and labor. Furthermore, we propose that during pregnancy the mechanical and hormonal stimuli play a role in regulating myometrial TGFβs. The expression of TGFβ1-3 mRNAs and proteins was examined by real-time PCR, Western immunoblot, and localized with immunohistochemistry in the rat uterus throughout pregnancy and labor. Tgfβ1-3 genes were expressed differentially in pregnant myometrium. Tgfβ2 gene was not affected by pregnancy, whereas the Tgfβ1 gene showed a threefold increase during the second half of gestation. In contrast, we observed a dramatic bimodal change in Tgfβ3 gene expression throughout pregnancy. Tgfβ3 mRNA levels first transiently increased at mid-gestation (11-fold on day 14) and later at term (45-fold at labor, day 23). Protein expression levels paralleled the changes in mRNA. Treatment of pregnant rats with the progesterone (P4) receptor antagonist RU486 induced premature labor on day 19 and increased Tgfβ3 mRNA, whereas artificial maintenance of elevated P4 levels at late gestation (days 20–23) caused a significant decrease in the expression of Tgfβ3 gene. In addition, Tgfβ3 was up-regulated specifically in the gravid horn of unilaterally pregnant rats subjected to a passive biological stretch imposed by the growing fetuses, but not in the empty horn. Collectively, these data indicate that the TGFβ family contributes in the regulation of myometrial activation at term integrating mechanical and endocrine signals for successful labor contraction.

Upregulation of osteopontin expression is involved in the development of nonalcoholic steatohepatitis in a dietary murine model

2004 ◽  
Vol 287 (1) ◽  
pp. G264-G273 ◽  
Author(s):  
Atul Sahai ◽  
Padmini Malladi ◽  
Hector Melin-Aldana ◽  
Richard M. Green ◽  
Peter F. Whitington
Keyword(s):  
Oxidative Stress ◽  
Mrna Expression ◽  
Nonalcoholic Steatohepatitis ◽  
Transforming Growth Factor ◽  
Control Diet ◽  
Transforming Growth Factor Β ◽  
Collagen I ◽  
Tnf Α ◽  
Th1 Cytokine

The pathogenesis of nonalcoholic steatohepatitis (NASH) is poorly defined. Feeding mice a diet deficient in methionine and choline (MCD diet) induces experimental NASH. Osteopontin (OPN) is a Th1 cytokine that plays an important role in several fibroinflammatory diseases. We examined the role of OPN in the development of experimental NASH. A/J mice were fed MCD or control diet for up to 12 wk, and serum alanine aminotransferase (ALT), liver histology, oxidative stress, and the expressions of OPN, TNF-α, and collagen I were assessed at various time points. MCD diet-fed mice developed hepatic steatosis starting after 1 wk and inflammation by 2 wk; serum ALT increased from day 3. Hepatic collagen I mRNA expression increased during 1–4 wk, and fibrosis appeared at 8 wk. OPN protein expression was markedly increased on day 1 of MCD diet and persisted up to 8 wk, whereas OPN mRNA expression was increased at week 4. TNF-α expression was increased from day 3 to 2 wk, and evidence of oxidative stress did not appear until 8 wk. Increased expression of OPN was predominantly localized in hepatocytes. Hepatocytes in culture also produced OPN, which was stimulated by transforming growth factor-β and TNF-α. Moreover, MCD diet-induced increases in serum ALT levels, hepatic inflammation, and fibrosis were markedly reduced in OPN−/− mice when compared with OPN+/+ mice. In conclusion, our results demonstrate an upregulation of OPN expression early in the development of steatohepatitis and suggest an important role for OPN in signaling the onset of liver injury and fibrosis in experimental NASH.

scholarly journals Acute Liver Injury after CCl4 Administration Is Independent of Smad7 Expression in Myeloid Cells

2019 ◽  
Vol 20 (22) ◽  
pp. 5528 ◽  
Author(s):  
Jessica Endig ◽  
Ludmilla Unrau ◽  
Paulina Sprezyna ◽  
Sebasting Rading ◽  
Meliha Karsak ◽  
...  
Keyword(s):  
Liver Injury ◽  
Transforming Growth Factor ◽  
Inflammatory Responses ◽  
Elevated Serum ◽  
Myeloid Cells ◽  
Transforming Growth Factor Β ◽  
Cellular Processes ◽  
Ccl4 Administration ◽  
Smad7 Expression ◽  
The Impact

Myeloid cells are essential for the initiation and termination of innate and adaptive immunity that create homeostasis in the liver. Smad7 is an inhibitor of the transforming growth factor β (TGF-β) signaling pathway, which regulates inflammatory cellular processes. Knockdown of Smad7 in hepatocytes has been shown to promote liver fibrosis, but little is known about the effects of Smad7 in myeloid cells during inflammatory responses in the liver. Using mice with a myeloid-specific knockdown of Smad7 (LysM-Cre Smad7fl/fl), we investigated the impact of Smad7 deficiency in myeloid cells on liver inflammation and regeneration using the well-established model of CCl4-mediated liver injury. Early (24/48 h) and late (7 d) time points were analyzed. We found that CCl4 induces severe liver injury, with elevated serum ALT levels, centrilobular and periportal necrosis, infiltrating myeloid cells and an increase of inflammatory cytokines in the liver. Furthermore, as expected, inflammation peaked at 24 h and subsided after 7 d. However, the knockdown of Smad7 in myeloid cells did not affect any of the investigated parameters in the CCl4-treated animals. In summary, our results suggest that the inhibition of TGF-β signaling via Smad7 expression in myeloid cells is dispensable for the induction and control of acute CCl4-induced liver injury.

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