The anti-inflammatory action of glucocorticoids is mediated by cell type specific regulation of apoptosis

Amsterdam, Abraham; Sasson, Ravid

doi:10.1016/s0303-7207(01)00722-5

Cited by 92 publications

(64 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Indeed, elevated Gc leads to rapid apoptotic loss of lymphoid cells both peripherally and in the bone marrow (12,21,29,30). Numerous studies have been undertaken to assess the effects of Gc on granulocyte function.…”

Section: Discussionmentioning

confidence: 99%

Natural glucocorticoids induce expansion of all developmental stages of murine bone marrow granulocytes without inhibiting function

Trottier

Newsted

King

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Natural glucocorticoids (Gc) produced during stress have profound effects on the immune system. It is well known that Gc induce apoptosis in precursor T and B cells, markedly altering lymphopoiesis. However, it has been noted that marrow myeloid cells expanded both in proportion and absolute numbers in the mouse after Gc exposure. Mice were implanted with a corticosterone (CS) tablet that increased serum Gc and caused atrophied thymuses, both classic signs of activation of the stress axis. Blood neutrophil counts were elevated (4.8؋), whereas lymphocyte counts declined. Flow cytometric analysis of the marrow revealed that the phenotypic distribution of the various major classes of cells was shifted by Gc exposure. As expected, marrow lymphocyte numbers declined >40% after 3 days of exposure to Gc. Conversely, in the myeloid compartment, both monocytes and granulocytes increased in number by >40%. Further, all granulocyte developmental stages showed large increases in both total number and percentage of cells. To investigate the functional capacity of mature granulocytes from Gc-treated mice, an improved granulocyte isolation method was developed. Gc exposure had little effect on the ability of granulocytes to produce superoxide or undergo chemotaxis or phagocytose bacteria. These results indicate that Gc treatment shifts bone marrow composition and provides evidence that granulocytes and their progenitors are selectively preserved under stressful conditions without losing function.granulopoiesis ͉ lymphopoiesis

show abstract

Section: Discussionmentioning

confidence: 99%

Natural glucocorticoids induce expansion of all developmental stages of murine bone marrow granulocytes without inhibiting function

Trottier

Newsted

King

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Furthermore, immune cells have been demonstrated to invade the porcine CL during PGF 2 -induced luteolysis [9]. Since the inflammatory response involves the actions of cytokines, which are produced by immune cells, and since many cytokines stimulate production of PGs by the cells of target organs [2], it is possible that the CL during luteolysis is subject to inflammatory-like conditions. Our previous study demonstrated that GC inhibits P and PGF 2 secretion by cultured porcine luteal cells [21].…”

Section: Discussionmentioning

confidence: 99%

“…Hypothalamic CRH induces adrenocorticotropic hormone (ACTH) secretion by the pituitary via its specific receptors (CRH-R), and the ACTH stimulates glucocorticoid (GC) production from the adrenal gland; this is considered to be the hypothalamicpituitary-adrenal (HPA) axis [22]. GC is produced in the adrenal cortex during periods of stress and is widely recognized as an immunosuppressive and anti-inflammatory agent [2]. It has been shown to inhibit expression of cytokines, adhesion molecules and enzymes involved in the inflammatory process [4].…”

mentioning

confidence: 99%

Possible Actions of Corticotropin-Releasing Hormone in Regulating Porcine Corpus Luteum Function

Sakumoto

Ito

Komatsu

2010

The Journal of Veterinary Medical Science

View full text Add to dashboard Cite

ABSTRACT. The objective of the present study was to determine whether corticotropin-releasing hormone (CRH) influences porcine corpus luteum function. The gene expressions of CRH receptors (CRH-R) were determined in the CLs of Chinese Meishan pigs during the estrous cycle. The effects of CRH on progesterone (P), estradiol-17 (E) and prostaglandin (PG) F 2 secretion by cultured luteal cells were also investigated. Messenger RNAs of the CRH-R were clearly expressed in the CL throughout the estrous cycle, and the mRNA level was higher at the regressed stage than at the other stages (P<0.05). When the cultured luteal cells obtained from the mid-luteal stage CL (days 8-11) were exposed to CRH (50-5000 ng/ml), P secretion by the cells was significantly reduced at the highest dose (P<0.05), whereas CRH had no effect on E and PGF 2 secretion by the cells. The overall results suggest that CRH inhibits local P production from luteal cells via its specific CRH-R, implying that CRH plays some roles in regulating porcine CL function during the estrous cycle, especially in the period of luteolysis.KEY WORDS: corpus luteum, corticotropin-releasing hormone, receptor, swine.J. Vet. Med. Sci. 72(9): 1173-1177, 2010 Corticotropin-releasing hormone (CRH) is known as a stress-induced peptide that is secreted from the paraventricular nucleus of the hypothalamus [22]. Hypothalamic CRH induces adrenocorticotropic hormone (ACTH) secretion by the pituitary via its specific receptors (CRH-R), and the ACTH stimulates glucocorticoid (GC) production from the adrenal gland; this is considered to be the hypothalamicpituitary-adrenal (HPA) axis [22]. GC is produced in the adrenal cortex during periods of stress and is widely recognized as an immunosuppressive and anti-inflammatory agent [2]. It has been shown to inhibit expression of cytokines, adhesion molecules and enzymes involved in the inflammatory process [4]. Our recent study demonstrated the presence of GC and its converting enzymes in the porcine corpus luteum (CL) and that GC inhibits steroid production from cultured luteal cells [21], suggesting that GC may regulate CL function locally in pigs.Recent studies indicate that a CRH/CRH-R system also exists outside the central nervous system. CRH and CRH-R have been identified in the human placenta [8,17], endometrium [11,12] and ovaries [3,14]. In monkeys, the genes and proteins for CRH and CRH-R are expressed in the CL during the menstrual cycle [24]. Moreover, CRH inhibits progesterone (P) and estradiol-17 (E) secretion by cultured human granulosa-lutein cells [7]. Since the E production from the CL in pigs is a specific feature that is similar to those of the CLs in humans and monkeys [23], the previous studies lead us to hypothesize that CRH directly regulates CL function in pigs as well as in primates.In the present study, therefore, we measured expression of CRH-R in the porcine CL from different stages of the estrous cycle using reverse transcription (RT) polymerase chain reaction (PCR) and real-time PCR analyses. The possible...

show abstract

“…The effects of glucocorticoids on cell death and survival depend on the cell type. For instance, these steroids induce apoptosis of cells involved in inflammatory reactions, such as monocytes, macrophages and T lymphocytes, but they protect some cells of epithelial origin against apoptotic signals [42]. Many studies have examined the effects of glucocorticoids on the function of beta cells.…”

Section: Discussionmentioning

confidence: 99%

Expression and secretion of alpha1-proteinase inhibitor are regulated by proinflammatory cytokines in human pancreatic islet cells

et al. 2005

View full text Add to dashboard Cite

Aims/hypothesis: Alpha1-proteinase inhibitor (α1-PI) has been considered a key player in inflammatory processes. In humans, the main production site of α1-PI is the liver, but other tissues, including pancreatic islets, also synthesise this molecule. The aims of this study were to assess the islet cell types that produce α1-PI, to determine whether α1-PI is actually secreted by islet cells, and to assess how its production and/or secretion are regulated. Methods: Expression of α1-PI in human islet cells was assessed by immunofluorescence, electron microscopy and western blotting. Release of α1-PI was analysed by reverse haemolytic plaque assay and ELISA. The effects of cytokines on α1-PI synthesis and secretion were tested. Results: Immunofluorescence showed that alpha and delta cells do express α1-PI, whereas beta cells do not. By electron microscopy, we demonstrated a colocalisation of α1-PI with glucagon and somatostatin within secretory granules. Immunolabelling also revealed localisation of α1-PI within the Golgi apparatus, related vesicles and lysosomal structures. The expression of α1-PI in islet cells was also demonstrated by western blotting and ELISA of protein extracts. ELISA and reverse haemolytic plaque assay showed that α1-PI is secreted into the culture medium. Treatment of islet cells with IL-1β and oncostatin M for 4 days increased the production and release of α1-PI. Conclusions/interpretation: Our results demonstrate that α1-PI is expressed by the alpha and delta cells of human islets, and that proinflammatory cytokines enhance the production and release of this inhibitor.Keywords Human islets . IL-1β . Oncostatin M . α1-Proteinase inhibitor . Reverse haemolytic plaque assay Abbreviations OSM: oncostatin M . α1-PI: alpha1-proteinase inhibitor . RHPA: reverse haemolytic plaque assay

show abstract

The anti-inflammatory action of glucocorticoids is mediated by cell type specific regulation of apoptosis

Cited by 92 publications

References 66 publications

Natural glucocorticoids induce expansion of all developmental stages of murine bone marrow granulocytes without inhibiting function

Natural glucocorticoids induce expansion of all developmental stages of murine bone marrow granulocytes without inhibiting function

Possible Actions of Corticotropin-Releasing Hormone in Regulating Porcine Corpus Luteum Function

Expression and secretion of alpha1-proteinase inhibitor are regulated by proinflammatory cytokines in human pancreatic islet cells

Contact Info

Product

Resources

About