Thymic peptides and neuroendocrine-immune communication

Millington, G. W. M.; Buckingham, Julia C.

doi:10.1677/joe.0.1330163

Cited by 37 publications

(52 citation statements)

References 22 publications

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“…The aforementioned results conspicuously affirm that thymulin can regulate the phosphorylation of IB- in the hippocampus, an observation corroborated elsewhere [4,9,11,37]. Of particular significance is the observation that thymulin can modulate the NF-B pathway via the differential down regulation of the nuclear translocation of various subunits, in addition to downregulating their activation [1].…”

Section: American Journal Of Medical and Biological Researchsupporting

confidence: 78%

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The Anti-Inflammatory and Immunomodulatory Activity of Thymulin Peptide is NF-κB-Dependent and Involves the Downregulation of IκB-α

Haddad¹,

Hanbali²

2013

AJMBR

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The immunomodulatory activity of thymulin and related analogues in vivo is not well characterized in the CNS. We have previously provided evidence for an anti-inflammatory potential of thymulin in downregulating proinflammatory cytokines in a NF-B-dependent mechanism in vitro. Furthermore, we have shown that intracerebroventricular (ICV) treatment with thymulin in the hippocampus (HC) reduced the nuclear localization and activation of NF-B, an effect mediated by the IB-α/pIB-α pathway in vivo. ICV stereotaxic injection of endotoxin (ET) differentially upregulated the nuclear translocation /expression of NF-B 1 (p50), NF-B 2 (p52), RelA (p65), RelB (p68) and c-Rel (p75) in the HC. Pretreatment with thymulin followed by ET exposure reduced the nuclear translocation of NF-B subunits. The anti-inflammatory effect of thymulin seems to be mediated via the IB- pathway since thymulin downregulated ET-induced phosphorylation of IB-. Stereotaxic pretreatment with synthetic peptide analogue of thymulin (PAT) reduced the nuclear translocation of NF-B subunits, an effect mediated by downregulating the phosphorylation of IB-. EMSA revealed dose-dependent inhibition of NF-B/DNA activation mediated by ICV ET. These results indicate that the anti-inflammatory effect of thymulin/PAT, mediated by IB-, is NF-B-dependent and involves the downregulation of the nuclear translocation of various NF-B subunits and their subcellular activation.

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Section: American Journal Of Medical and Biological Researchsupporting

confidence: 78%

“…Thymulin, a nonapeptide hormone secreted by the thymus essentially for regulating T lymphocyte differentiation and function, has major antiinflammatory and immunomodulatory properties [2], thereby it provides an interface between neuroendocrineimmune communication systems [3,4].…”

Section: Introductionmentioning

confidence: 99%

The Anti-Inflammatory and Immunomodulatory Activity of Thymulin Peptide is NF-κB-Dependent and Involves the Downregulation of IκB-α

Haddad¹,

Hanbali²

2013

AJMBR

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“…However, the interconnections among the immune, nervous, and endocrine systems are substantial, with innervation of lymphoid organs and receptors for all major endocrine axes on lymphocytes as well as lymphoid tissues. Indeed, these reciprocal connections are so pervasive, and so critical to immune development and function, that immune function is conceptualized as part of a seamless neuro-immune-endocrine network (Ader et al, 2001;Besedovsky and del Rey, 1991;Cotman et al, 1987;Imura et al, 1991;Millington and Buckingham, 1992). These connections provide a number of potential physiological mechanisms through which life-history trade-offs involving immunity may be mediated.…”

Section: Human Immune Functionmentioning

confidence: 99%

Life history theory and the immune system: Steps toward a human ecological immunology

McDade¹

2003

Am. J. Phys. Anthropol.

284

305

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KEY WORDSimmunology; human biology; growth and development; evolutionary theory; infectious disease ABSTRACTWithin anthropology and human biology, there is growing interest in immune function and its importance to the ecology of human health and development. Biomedical research currently dominates our understanding of immunology, and this paper seeks to highlight the potential contribution of a population-based, ecological approach to the study of human immune function. Concepts from life-history theory are applied to highlight the major challenges and demands that are likely to shape immune function in a range of ecological contexts. Immune function is a major component of maintenance effort, and since resources are limited, trade-offs are expected between investment in maintenance and other critical life-history functions involving growth and reproduction. An adaptationist, life-history perspective helps make sense of the unusual developmental trajectory of immune tissues, and emphasizes that this complex system is designed to incorporate information from the surrounding ecology to guide its development. As a result, there is substantial population variation in immune development and function that is not considered by current biomedical approaches. In an attempt to construct a framework for understanding this variation, immune development is considered in relation to the competing life-history demands that define gestation, infancy, childhood, adolescence, and adulthood. Each life stage poses a unique set of adaptive challenges, and a series of hypotheses is proposed regarding their implications for immune development and function. Research in human ecological immunology is in its earliest stages, but this is a promising area of exploration, and one in which anthropology is wellpositioned to make important contributions. Yrbk Phys Research on human immune function has proliferated in the past 25 years, leading to fundamental insights into basic physiology, as well as strategies for the prevention and treatment of a wide range of diseases. The complexity of the immune system is daunting, and current biomedical research elaborates this complexity by focusing almost exclusively on cellular-and molecular-level processes. The majority of this research uses animal models, with human research participants drawn primarily from clinical settings. Complementary population-based research in international health has observed consistent, bidirectional associations between undernutrition and infectious morbidity, sparking interest in immunocompetence as a potentially important mediator (Chandra, 1988;Gershwin et al., 2000;Hoffman-Goetz, 1986;Pelletier et al., 1995;Suskind and Tontisirin, 2001).The significance of these contributions should not be overlooked, but something is missing. Human physiological systems are products of natural selection, designed to develop and function in whole organisms that are integral components of surrounding social and physical environments (Oyama, 1985;Williams and Nesse, 1991). The immune s...

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“…TEC are potential targets of neuroendocrine ligands present in the circulation [33][34][35] and of input from the thymic innervation [36][37][38][39]. Ionic mechanisms of TEC have previously been implicated in thymulin secretion [40,41].…”

Section: Discussionmentioning

confidence: 99%

Rapid Progesterone Actions on Thymulin-Secreting Epithelial Cells Cultured from Rat Thymus

Head

Downing

Brucker

et al. 1999

Neuroimmunomodulation

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Many soluble factors of neural, endocrine, paracrine and autocrine origin are present in the thymus and modulate its function. Long-term effects of sex steroids have been documented for thymocytes and cells of the thymic microenvironment. In this report we examine rapid actions of progesterone upon aspects of epithelial cell physiology. Progesterone (0.1–10 µM) was applied to cultured thymulin-secreting thymic epithelial cells (TS-TEC) and changes in transmembrane potential, transmembrane current, intracellular calcium levels and thymulin secretion were assessed. Rapid changes in electrophysiology and intracellular calcium provide evidence for a membrane-bound progesterone receptor in these cells, in addition to classical cytoplasmic receptors. Application of progesterone to TS-TEC caused electrophysiological changes in 56% of cells (n = 40), activating an inward current (–24 ± 9 pA at 1 µM, n = 7, p < 0.02) and dose-dependent depolarization (7.1 ± 1.8 mV at 1 µM, n = 19, p < 0.01). Intracellular calcium levels, monitored by the ratiometric fluorescent calcium indicator fura-2, increased within seconds of progesterone (1 µM) application. Progesterone (1 µM) increased thymulin levels in supernatant, as measured by ELISA, above the levels in the preapplication period (142 ± 16% of the preapplication period, n = 3, p < 0.02). This effect was reduced in the presence of cobalt chloride which blocks voltage-dependent calcium channels. In addition, TS-TEC in culture were immunoreactive to antibody AG7. This antibody was raised to a membrane-bound antigen involved in calcium influx subsequent to progesterone binding in sperm. Thus we suggest that progesterone acts upon many aspects of TS-TEC physiology through both cytoplasmic and membrane-bound receptors.

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Thymic peptides and neuroendocrine-immune communication

Cited by 37 publications

References 22 publications

The Anti-Inflammatory and Immunomodulatory Activity of Thymulin Peptide is NF-κB-Dependent and Involves the Downregulation of IκB-α

The Anti-Inflammatory and Immunomodulatory Activity of Thymulin Peptide is NF-κB-Dependent and Involves the Downregulation of IκB-α

Life history theory and the immune system: Steps toward a human ecological immunology

Rapid Progesterone Actions on Thymulin-Secreting Epithelial Cells Cultured from Rat Thymus

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Thymic peptides and neuroendocrine-immune communication

Cited by 37 publications

References 22 publications

The Anti-Inflammatory and Immunomodulatory Activity of Thymulin Peptide is NF-&#954;B-Dependent and Involves the Downregulation of I&#954;B-&#945;

The Anti-Inflammatory and Immunomodulatory Activity of Thymulin Peptide is NF-&#954;B-Dependent and Involves the Downregulation of I&#954;B-&#945;

Life history theory and the immune system: Steps toward a human ecological immunology

Rapid Progesterone Actions on Thymulin-Secreting Epithelial Cells Cultured from Rat Thymus

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The Anti-Inflammatory and Immunomodulatory Activity of Thymulin Peptide is NF-κB-Dependent and Involves the Downregulation of IκB-α

The Anti-Inflammatory and Immunomodulatory Activity of Thymulin Peptide is NF-κB-Dependent and Involves the Downregulation of IκB-α