Distinct regulation by lipopolysaccharides of the expression of interleukin-1β by murine macrophages and salivary glands

2010 ◽  
Vol 18 (1) ◽  
pp. 14-24 ◽  
Author(s):  
M Seil ◽  
M El Ouaaliti ◽  
S Abdou Foumekoye ◽  
S Pochet ◽  
JP Dehaye
Keyword(s):  
Salivary Glands ◽  
Submandibular Gland ◽  
Adenosine Triphosphate ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Wild Type ◽  
Murine Macrophages ◽  
Lower Volume ◽  
Submandibular Acini ◽  
Salivary Concentration

The regulation of interleukin (IL)-1 expression and secretion by salivary glands and macrophages in response to lipopolysaccharides (LPS) was compared. In wild-type mice, injection of LPS significantly decreased the volume of saliva stimulated by pilocarpine and increased its protein and amylase concentration. It did not modify the salivary concentration of IL-1β. The cytokine was expressed by submandibular acini and ducts. Macrophages also expressed IL-1β but at lower concentration than salivary glands. The pre-incubation of macrophages with LPS increased the phosphorylation of IκB and the expression of IL-1β. Adenosine triphosphate also promoted the secretion of the cytokine by these cells. These responses were absent in submandibular gland cells. These glands expressed CD14, TLR4 and MyD88. P2X7-KO mice secreted a lower volume of saliva which contained less proteins and amylase. In conclusion, IL-1β is constitutively expressed by submandibular glands and its secretion is not regulated by a P2X7 agonist. In these cells, LPS do not activate the nuclear factor-κB–pro-IL-1β axis in spite of the expression of the proteins involved in their recognition.

scholarly journals Oxidative Stress Transiently Decreases the IKK Complex (IKKα, β, and γ), an Upstream Component of NF-κB Signaling, after Transient Focal Cerebral Ischemia in Mice

2005 ◽  
Vol 25 (10) ◽  
pp. 1301-1311 ◽  
Author(s):  
Yun S Song ◽  
Yong-Sun Lee ◽  
Pak H Chan
Keyword(s):  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Dna Array ◽  
Wild Type ◽  
Iκb Kinase ◽  
Transient Focal Cerebral Ischemia ◽  
Ikk Complex ◽  
In The Wild

Nuclear factor-κB (NF-κB) has a central role in coordinating the expression of a wide variety of genes that control cerebral ischemia. Although there has been intense research on NF-κB, its mechanisms in the ischemic brain have not been clearly elucidated. We investigated the temporal profile of NF-κB-related genes using a complementary DNA array method in wild-type mice and human copper/zinc-superoxide dismutase transgenic (SOD1 Tg) mice that had low-level reactive oxygen species (ROS) by scavenging superoxide. Our DNA array showed that IκB kinase (IKK) complex (IKKα, β, and γ) mRNA in the wild-type mice was decreased as early as 1 h after reperfusion, after 30 mins of transient focal cerebral ischemia (tFCI). In contrast, tFCI in the SOD1 Tg mice caused an increase in the IKK complex. The IKK complex protein levels were also drastically decreased at 1 h in the wild-type mice, but did not change in the SOD1 Tg mice throughout the 7 days. Electrophoretic mobility shift assay revealed activation of NF-κB DNA binding after tFCI in the wild-type mice. Nuclear factor-κB activation occurred at the same time, as did the phosphorylation and degradation of the inhibitory protein κBα. However, SOD1 prevented NF-κB activation, and phosphorylation and degradation of IκBα after tFCI. Superoxide production and ubiquitinated protein in the SOD1 Tg mice were also lower than in the wild-type mice after tFCI. These results suggest that ROS are implicated in transient downregulation of IKKα, β, and γ in cerebral ischemia.

scholarly journals Hyaluronan Fragments Induce Nitric-oxide Synthase in Murine Macrophages through a Nuclear Factor κB-dependent Mechanism

1997 ◽  
Vol 272 (12) ◽  
pp. 8013-8018 ◽  
Author(s):  
Charlotte M. McKee ◽  
Charles J. Lowenstein ◽  
Maureen R. Horton ◽  
Jean Wu ◽  
Clare Bao ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Murine Macrophages ◽  
Oxide Synthase ◽  
Dependent Mechanism

scholarly journals A Role for Site-Specific Phosphorylation of Mouse Progesterone Receptor at Serine 191 in Vivo

2014 ◽  
Vol 28 (12) ◽  
pp. 2025-2037 ◽  
Author(s):  
Sandra L. Grimm ◽  
Robert D. Ward ◽  
Alison E. Obr ◽  
Heather L. Franco ◽  
Rodrigo Fernandez-Valdivia ◽  
...  
Keyword(s):  
Mammary Epithelial Cells ◽  
Phosphorylation Site ◽  
Three Dimensional ◽  
Progesterone Receptors ◽  
Nuclear Factor Κb ◽  
Mammary Epithelial ◽  
Nuclear Factor ◽  
Wild Type ◽  
Receptor Activator

Progesterone receptors (PRs) are phosphorylated on multiple sites, and a variety of roles for phosphorylation have been suggested by cell-based studies. Previous studies using PR-null mice have shown that PR plays an important role in female fertility, regulation of uterine growth, the uterine decidualization response, and proliferation as well as ductal side-branching and alveologenesis in the mammary gland. To study the role of PR phosphorylation in vivo, a mouse was engineered with homozygous replacement of PR with a PR serine-to-alanine mutation at amino acid 191. No overt phenotypes were observed in the mammary glands or uteri of PR S191A treated with progesterone (P4). In contrast, although PR S191A mice were fertile, litters were 19% smaller than wild type and the estrous cycle was lengthened slightly. Moreover, P4-dependent gene regulation in primary mammary epithelial cells (MECs) was altered in a gene-selective manner. MECs derived from wild type and PR S191A mice were grown in a three-dimensional culture. Both formed acinar structures that were morphologically similar, and proliferation was stimulated equally by P4. However, P4 induction of receptor activator of nuclear factor-κB ligand and calcitonin was selectively reduced in S191A cultures. These differences were confirmed in freshly isolated MECs. Chromatin immunoprecipitation analysis showed that the binding of S191A PR to some of the receptor activator of nuclear factor-κB ligand enhancers and a calcitonin enhancer was substantially reduced. Thus, the elimination of a single phosphorylation site is sufficient to modulate PR activity in vivo. PR contains many phosphorylation sites, and the coordinate regulation of multiple sites is a potential mechanism for selective modulation of PR function.

scholarly journals Overexpression of an enzymically inactive interleukin-1-receptor-associated kinase activates nuclear factor-κB

1999 ◽  
Vol 339 (2) ◽  
pp. 227-231 ◽  
Author(s):  
Barbara MASCHERA ◽  
Keith RAY ◽  
Kimberly BURNS ◽  
Filippo VOLPE
Keyword(s):  
Kinase Activity ◽  
Interleukin 1 ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Wild Type ◽  
Defective Mutant ◽  
Asparagine Residue

Upon interleukin 1 (IL-1) stimulation, the IL-1-receptor (IL-1R)-associated kinase (IRAK) is rapidly recruited to the IL-1R complex and undergoes phosphorylation. Here we demonstrate that recombinant wild-type IRAK (IRAK-WT), but not a kinase-defective mutant with Asp340 replaced by an asparagine residue (IRAK-Asp340Asn), is highly phosphorylated and is capable of auto-phosphorylation in vitro. Overexpression of both IRAK-WT and IRAK-Asp340Asn caused activation of nuclear factor κB, suggesting that the kinase activity of IRAK is not required outside of the IL-1R complex.

Lipopolysaccharide activates ERK–PARP-1–RelA pathway and promotes nuclear factor–κB transcription in murine macrophages

2012 ◽  
Vol 73 (5) ◽  
pp. 439-447 ◽  
Author(s):  
Linlin Liu ◽  
Yueshuang Ke ◽  
Xue Jiang ◽  
Fen He ◽  
Lang Pan ◽  
...  
Keyword(s):  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Murine Macrophages ◽  
Parp 1

scholarly journals Deletion of IGF-1 Receptors in Cardiomyocytes Attenuates Cardiac Aging in Male Mice

Endocrinology ◽  
2016 ◽  
Vol 157 (1) ◽  
pp. 336-345 ◽  
Author(s):  
Sangmi Ock ◽  
Wang Soo Lee ◽  
Jihyun Ahn ◽  
Hyun Min Kim ◽  
Hyun Kang ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Wild Type ◽  
Hypertrophic Response ◽  
Age Related ◽  
Receptor Activator ◽  
Phosphoinositide 3 Kinase ◽  
Cultured Cardiomyocytes

Abstract IGF-1 receptor (IGF-1R) signaling is implicated in cardiac hypertrophy and longevity. However, the role of IGF-1R in age-related cardiac remodeling is only partially understood. We therefore sought to determine whether the deletion of the IGF-1R in cardiomyocytes might delay the development of aging-associated myocardial pathologies by examining 2-year-old male cardiomyocyte-specific IGF-1R knockout (CIGF1RKO) mice. Aging was associated with the induction of IGF-1R expression in hearts. Cardiomyocytes hypertrophied with age in wild-type (WT) mice. In contrast, the cardiac hypertrophic response associated with aging was blunted in CIGF1RKO mice. Concomitantly, fibrosis was reduced in aged CIGF1RKO compared with aged WT hearts. Expression of proinflammatory cytokines such as IL-1α, IL-1β, IL-6, and receptor activator of nuclear factor-κB ligand was increased in aged WT hearts, but this increase was attenuated in aged CIGF1RKO hearts. Phosphorylation of Akt was increased in aged WT, but not in aged CIGF1RKO, hearts. In cultured cardiomyocytes, IGF-1 induced senescence as demonstrated by increased senescence-associated β-galactosidase staining, and a phosphoinositide 3-kinase inhibitor inhibited this effect. Furthermore, inhibition of phosphoinositide 3-kinase significantly prevented the increase in IL-1α, IL-1β, receptor activator of nuclear factor-κB ligand, and p21 protein expression by IGF-1. These data reveal an essential role for the IGF-1-IGF-1R-Akt pathway in mediating cardiomyocyte senescence.

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