scholarly journals Activation of Phosphatidylinositol 3-Kinase/Protein Kinase B by Corticotropin-Releasing Factor in Human Monocytes

Endocrinology ◽  
2009 ◽  
Vol 150 (10) ◽  
pp. 4606-4614 ◽  
Author(s):  
Christina Chandras ◽  
Yassemi Koutmani ◽  
Efi Kokkotou ◽  
Charalabos Pothoulakis ◽  
Katia P. Karalis
Keyword(s):  
Cell Survival ◽  
Inflammatory Diseases ◽  
Nuclear Factor Κb ◽  
Binding Activity ◽  
Corticotropin Releasing Factor ◽  
Human Monocytes ◽  
Phosphatidylinositol 3 Kinase ◽  
Peripheral Tissues ◽  
Dna Binding Activity ◽  
Phosphatidylinositol 3

Abstract Corticotropin-releasing factor (CRF) exerts proinflammatory effects in peripheral tissues, whereas the intracellular pathways mediating these effects have not been completely characterized yet. We have previously shown that CRF induces nuclear factor-κB DNA-binding activity in mouse and human leukocytes. Here we demonstrate that in the human monocytic THP-1 cells, CRF activates the phosphatidylinositol 3-kinase (PI3K)/Akt and ERK1/2 pathways. These effects of CRF are mediated by corticotropin-releasing factor receptor 2 (CRF2), as suggested by their abolishment after treatment with the specific CRF2 antagonist, astressin 2B. The CRF-mediated PI3K/Akt activation induces cell survival as suggested by the stimulation of the antiapoptotic factor Bcl-2. ERK1/2 activation results in up-regulation of IL-8 expression, an effect inhibited by the CRF-induced activation of PI3K/Akt. These studies demonstrate novel effects of CRF in human monocytes mediated by the activation of PI3K/Akt. Moreover, they reveal pathway-specific effects of the CRF/CRF2 system in chemokine activation and cell survival that may be of importance for the development of novel therapeutics for inflammatory diseases.

scholarly journals Interferon α/β Promotes Cell Survival by Activating Nuclear Factor κB through Phosphatidylinositol 3-Kinase and Akt

2001 ◽  
Vol 276 (17) ◽  
pp. 13756-13761 ◽  
Author(s):  
Chuan He Yang ◽  
Aruna Murti ◽  
Susan R. Pfeffer ◽  
Jong G. Kim ◽  
David B. Donner ◽  
...  
Keyword(s):  
Cell Survival ◽  
Nuclear Factor Κb ◽  
Interferon Α ◽  
Nuclear Factor ◽  
Phosphatidylinositol 3 Kinase ◽  
Phosphatidylinositol 3

scholarly journals Expression and Deoxyribonucleic Acid-Binding Activity of the Nuclear Factor κB Family in the Human Myometrium during Pregnancy and Labor

2004 ◽  
Vol 89 (11) ◽  
pp. 5683-5693 ◽  
Author(s):  
Neil R. Chapman ◽  
G. Nicholas Europe-Finner ◽  
Stephen C. Robson
Keyword(s):  
Transcription Factors ◽  
Deoxyribonucleic Acid ◽  
Nuclear Factor Κb ◽  
Binding Activity ◽  
Akt Pathway ◽  
Human Myometrium ◽  
Nuclear Factor ◽  
Phosphatidylinositol 3 Kinase ◽  
Dna Binding Activity ◽  
Proinflammatory Factors

Abstract In humans, the factors that govern the switch from myometrial quiescence to coordinated contractions at the initiation of labor are not well defined. The onset of parturition is itself associated with increases in a number of proinflammatory factors, many of which are regulated by the nuclear factor κB (NF-κB) family of transcription factors. The expression and DNA-binding activity of NF-κB in the myometrium during gestation and parturition were examined. Levels of c-Rel, p50, and p105 NF-κB species were dramatically reduced in pregnant myometrium compared with nonpregnant (NP) controls, whereas expression of the RelA subunit remained uniform. Importantly, during labor, expression of all subunits was observed to be significantly reduced in all myometrial samples studied relative to NP levels. Moreover, for RelA, c-Rel, and p50 subunits, there was a gradient of expression between laboring upper (corpus) and lower uterine segment myometrium. No RelB or p52 subunits could be detected. EMSAs identified changes in NF-κB subunit composition in the myometrium during pregnancy and labor, with p50 homodimers predominant in NP tissues being replaced with RelA:p50 heterodimers in pregnant and laboring samples. Significantly, RelA was observed to be phosphorylated at serine-536, implicating the involvement of the phosphatidylinositol-3-kinase/AKT pathway in NF-κB function in the myometrium.

Ligation of CD11b and CD11c β2 integrins by antibodies or soluble CD23 induces macrophage inflammatory protein 1α (MIP-1α) and MIP-1β production in primary human monocytes through a pathway dependent on nuclear factor–κB

Blood ◽  
2001 ◽  
Vol 97 (10) ◽  
pp. 2932-2940 ◽  
Author(s):  
Roger Rezzonico ◽  
Veronique Imbert ◽  
Rachel Chicheportiche ◽  
Jean-Michel Dayer
Keyword(s):  
Dna Binding ◽  
Nuclear Factor Κb ◽  
Binding Activity ◽  
Nuclear Factor ◽  
Human Monocytes ◽  
Β2 Integrin ◽  
Dna Binding Activity ◽  
Inflammatory Protein ◽  
Macrophage Inflammatory Protein ◽  
Β2 Integrins

Abstract Chemokines and adhesion molecules such as integrins play a major part in the trafficking, extravasation, and recruitment of leukocytes to inflammatory sites. This study investigated the effects of β2 integrin engagement on chemokine production by freshly isolated human monocytes. We found that ligation of CD11b or CD11c but not CD11a α chains of β2 integrins by antibodies or soluble CD23 (sCD23) fusion proteins rapidly induced transcription and secretion of interleukin 8, macrophage inflammatory protein (MIP) 1α, and MIP-1β. Because the promoters of these chemokine genes contain κB binding sites, we assessed the possible role of nuclear factor–κB (NF-κB) in controlling induction of the genes through β2 integrin engagement. Electrophoretic mobility shift assays showed that sCD23 or antibodies to CD11b or to CD11c up-regulated DNA-binding activity of NF-κB. Activation of NF-κB was accompanied by degradation of its cytosolic inhibitor IκB-α. Blockade of depletion of IκB-α by proteasome inhibitors (proteasome inhibitor I or acetyl-leucinyl-leucinyl-norleucinal) led to concomitant inhibition of NF-κB DNA-binding activity and expression of MIP-1α and MIP-1β messenger RNA induced by β2 integrin ligation. These results suggest that triggering of CD11b or CD11c β2 integrin on primary human monocytes provides activation signals leading to nuclear translocation of NF-κB and subsequent secretion of MIP-1α and MIP-1β that may have an important role in recruitment of other inflammatory cells during initiation of an inflammatory response.

UV stimulation induces nuclear factor κB (NF-κB) DNA-binding activity but not transcriptional activation

2001 ◽  
Vol 29 (6) ◽  
pp. 688-691 ◽  
Author(s):  
K. J. Campbell ◽  
N. R. Chapman ◽  
N. D. Perkins
Keyword(s):  
Dna Binding ◽  
Transcriptional Activation ◽  
Cellular Response ◽  
Uv Light ◽  
Binding Protein ◽  
Nuclear Factor Κb ◽  
Camp Response Element Binding ◽  
Binding Activity ◽  
Nuclear Factor ◽  
Dna Binding Activity

The cellular response to DNA-damaging agents is partly mediated by DNA-binding transcription factors such as p53 and nuclear factor κB (NF-κB). Typically NF-κB activation is associated with resistance to apoptosis. Following stimulation with UV light however, NF-κB activation has been shown to be required for programmed cell death. To study this effect further and to determine the relationship between NF-κB and p53 function, we have examined the effect of UV light on U2OS cells. UV stimulation resulted in the activation of NF-κB DNA-binding and the induction of p53. Surprisingly, and in contrast with tumour necrosis factor α stimulation, this UV-induced NF-κB was transcriptionally inert. These observations suggest a model in which the NF-κB switch from an anti-apoptotic to a pro-apoptotic role within the cell results from modulation of its ability to stimulate gene expression, possibly as a result of the ability of p53 to sequester transcriptional co-activator proteins such as p300/CREB (cAMP-response-element-binding protein)-binding protein.

p65 controls NF-κB activity by regulating cellular localization of IκBβ

2011 ◽  
Vol 434 (2) ◽  
pp. 253-263 ◽  
Author(s):  
Taras Valovka ◽  
Michael O. Hottiger
Keyword(s):  
Dna Binding ◽  
Nuclear Export ◽  
Cellular Localization ◽  
Nuclear Export Signal ◽  
Nuclear Factor Κb ◽  
Binding Activity ◽  
Cellular Processes ◽  
Dna Binding Activity ◽  
Localization Signal ◽  
Export Signal

NF-κB (nuclear factor κB) controls diverse cellular processes and is frequently misregulated in chronic immune diseases or cancer. The activity of NF-κB is regulated by IκB (inhibitory κB) proteins which control nuclear–cytoplasmic shuttling and DNA binding of NF-κB. In the present paper, we describe a novel role for p65 as a critical regulator of the cellular localization and functions of NF-κB and its inhibitor IκBβ. In genetically modified p65−/− cells, the localization of ectopic p65 is not solely regulated by IκBα, but is largely dependent on the NLS (nuclear localization signal) and the NES (nuclear export signal) of p65. Furthermore, unlike IκBα, IκBβ does not contribute to the nuclear export of p65. In fact, the cellular localization and degradation of IκBβ is controlled by the p65-specific NLS and NES. The results of our present study also reveal that, in addition to stimulus-induced redistribution of NF-κB, changes in the constitutive localization of p65 and IκBβ specifically modulate activation of inflammatory genes. This is a consequence of differences in the DNA-binding activity and signal responsiveness between the nuclear and cytoplasmic NF-κB–IκBβ complexes. Taken together, the findings of the present study indicate that the p65 subunit controls transcriptional competence of NF-κB by regulating the NF-κB/IκBβ pathway.

scholarly journals TC21 mediates transformation and cell survival via activation of phosphatidylinositol 3-kinase/Akt and NF-κB signaling pathway

Oncogene ◽  
2002 ◽  
Vol 21 (7) ◽  
pp. 1062-1070 ◽  
Author(s):  
Rong Rong ◽  
Qin He ◽  
Yusen Liu ◽  
M Saeed Sheikh ◽  
Ying Huang
Keyword(s):  
Cell Survival ◽  
Signaling Pathway ◽  
Phosphatidylinositol 3 Kinase ◽  
Phosphatidylinositol 3
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