Acute thymic involution in fetuses and neonates with chorioamnionitis

Toti, Paolo; Felice, Claudio De; Stumpo, Michela; Schürfeld, Karin; Leo, Luigi; Vatti, Rosella; Bianciardi, Giorgio; Buonocore, Giuseppe; Seemayer, Thomas A.; Luzi, Pietro

doi:10.1053/hupa.2000.16676

Cited by 127 publications

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“…6 In the immune system, apart from the sympathetic nervous innervation of lymphoid organs, lymphocytes and macrophages themselves can be a source of catecholamines. 4,24 This is known to contribute to thymocyte apoptosis and thymic involution can exert immune-modulatory effect as a prototypic stress response. 24 The present work is the first demonstration of the molecular pathway of bAR-mediated apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…4,24 This is known to contribute to thymocyte apoptosis and thymic involution can exert immune-modulatory effect as a prototypic stress response. 24 The present work is the first demonstration of the molecular pathway of bAR-mediated apoptosis. Understanding the molecular mechanism of this apoptotic pathway may provide critical clues for developing new drugs for the treatment of diseases associated with increased b-adrenergic activation.…”

Section: Discussionmentioning

confidence: 99%

“…#P ¼ 0.004; *P ¼ 0.023 versus untreated control (b); #P ¼ 0.002-0.0012 versus untreated control (c); #P ¼ 0.0014 versus untreated control (d); #P ¼ 0.013 versus wild-type (WT) control gland, and this is attributed to increased secretion of catecholamines by the sympathetic nervous system. 24 As Bim is critical for the killing of thymocytes by diverse apoptotic stimuli, 11 we tested whether thymocytes could upregulate Bim in response to catecholamines. Treatment of thymocytes in foetal thymic organ culture (FTOC) with isoproterenol resulted in a robust induction of Nur77, a marker for PKA activation 25 and Bim, whereas the expression of other BH3-only genes, such as Puma (Bbc3) and Noxa remained unchanged (Figure 1c).…”

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confidence: 99%

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CREB-binding protein (CBP) regulates β-adrenoceptor (β-AR)−mediated apoptosis

et al. 2013

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Catecholamines regulate the b-adrenoceptor/cyclic AMP-regulated protein kinase A (cAMP/PKA) pathway. Deregulation of this pathway can cause apoptotic cell death and is implicated in a range of human diseases, such as neuronal loss during aging, cardiomyopathy and septic shock. The molecular mechanism of this process is, however, only poorly understood. Here we demonstrate that the b-adrenoceptor/cAMP/PKA pathway triggers apoptosis through the transcriptional induction of the pro-apoptotic BH3-only Bcl-2 family member Bim in tissues such as the thymus and the heart. In these cell types, the catecholamine-mediated apoptosis is abrogated by loss of Bim. Induction of Bim is driven by the transcriptional co-activator CBP (CREB-binding protein) together with the proto-oncogene c-Myc. Association of CBP with c-Myc leads to altered histone acetylation and methylation pattern at the Bim promoter site. Our findings have implications for understanding pathophysiology associated with a deregulated neuroendocrine system and for developing novel therapeutic strategies for these diseases. Cell Death and Differentiation (2013) 20, 941-952; doi:10.1038/cdd.2013 published online 12 April 2013 Cyclic adenosine monophosphate (cAMP) is a second messenger that is highly conserved throughout evolution. In metazoans, its primary role is to act as an intracellular carrier of metabolic information, regulating hormonal responses, 1 in triggering apoptotic cell death and in regulating ontogeny.2,3

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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CREB-binding protein (CBP) regulates β-adrenoceptor (β-AR)−mediated apoptosis

et al. 2013

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“…In addition, significant morphological changes are present in the thymus that include increased organ complexity, severe reduction of thymocytes, and monocytic and macrophagic infiltration of Hassall's bodies. 45 We have shown using the model of endotoxin-induced chorioamnionitis how the induction of a fetal inflammatory response resulted in changes in the thymus composition with respect to CD4-, CD8-and CD4/CD25-positive T lymphocytes. The latter T lymphocytes are regulatory T lymphocytes that have a major role in the initiation and resolution of inflammation.…”

Section: Thymusmentioning

confidence: 99%

Chorioamnionitis: a multiorgan disease of the fetus?

et al. 2010

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The bacterial infection of chorion and amnion is a common finding in premature delivery and is referred to as chorioamnionitis. As the mother rarely shows symptoms of a systemic inflammation, the course of chorioamnionitis is frequently asymptomatic and chronic. In contrast, the fetal inflammatory response syndrome represents a separate phenomenon, including umbilical inflammation and increased serum levels of proinflammatory cytokines in the fetus. Ascending maternal infections frequently lead to systemic fetal inflammatory reaction. Clinical studies have shown that antenatal exposure to inflammation puts the extremely immature neonates at a high risk for worsening pulmonary, neurological and other organ development. Interestingly, the presence of chorioamnionitis is associated with a lower rate of neonatal mortality in extremely immature newborns. In the following review, the pathogeneses of inflammation-associated perinatal morbidity are outlined. The concept of fetal multiorganic disease during intrauterine infection is introduced and discussed.

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“…After this point, it involutes slowly during further aging (Aspinall and Andrew 2000). In contrast, ATI is usually seen during gestational (Ekin et al 2016;Jacques et al 2014Jacques et al , 2015 and neonatal life (Eriksen et al 2014;Nickels et al 2015;Toti et al 2000) in humans. However, ATI in experimental animal models has been reported to occur not only during gestational periods (Kunzmann et al 2010;between ATI in adult experimental subjects and ageassociated thymic atrophy during the mid-phase of life in human beings is that the former occurs due to an increase in the death of thymocytes and has the ability to recover after the removal of the insult (Duan et al 2015;Lee et al 2011;Park et al 2007), whereas the latter is characterized by the substitution of lymphoid tissue with fat (adipose tissue) in a progressive time-dependent manner (Bodey et al 1997;Henry and Anderson 1987;Quaglino et al 2014).…”

Section: Introductionmentioning

confidence: 99%