Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 4 de 4
Filter
Add more filters










Database
Language
Publication year range
1.
Mucosal Immunol ; 6(1): 136-45, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22763408

ABSTRACT

The molecular mechanisms that restore intestinal epithelial homeostasis during colitis are incompletely understood. Here, we report that during intestinal inflammation, multiple inflammatory cytokines promote the activity of a master regulator of cell proliferation and apoptosis, serine/threonine kinase CK2. Enhanced mucosal CK2 protein expression and activity were observed in animal models of chronic colitis, particularly within intestinal epithelial cells (IECs). The in vitro treatment of intestinal epithelial cell lines with cytokines resulted in increased CK2 expression and nuclear translocation of its catalytic α subunit. Similarly, nuclear translocation of CK2α was a prominent feature observed in colonic crypts from individuals with ulcerative colitis and Crohn's disease. Further in vitro studies revealed that CK2 activity promotes epithelial restitution, and protects normal IECs from cytokine-induced apoptosis. These observations identify CK2 as a key regulator of homeostatic properties of the intestinal epithelium that serves to promote wound healing, in part through inhibition of apoptosis under conditions of inflammation.


Subject(s)
Casein Kinase II/metabolism , Colitis/immunology , Colitis/metabolism , Homeostasis/immunology , Intestinal Mucosa/immunology , Intestinal Mucosa/metabolism , Animals , Apoptosis/genetics , Casein Kinase II/genetics , Caspases/metabolism , Cell Line , Cell Nucleus/metabolism , Cell Proliferation , Colitis/chemically induced , Colitis/genetics , Disease Models, Animal , Epithelial Cells/metabolism , Gene Expression Regulation , Humans , Mice , Protein Transport , Rats , Wound Healing , beta Catenin/metabolism
2.
Mucosal Immunol ; 5(6): 681-90, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22692453

ABSTRACT

Proinflammatory cytokines induce guanylate-binding protein 1 (GBP-1) protein expression in intestinal epithelial tissues. GBP-1 has been described as influencing a number of cellular processes important for epithelial homeostasis, including cell proliferation. However, many questions remain as to the role of GBP-1 in intestinal mucosal homeostasis. We therefore sought to investigate the function of proinflammatory cytokine-induced GBP-1 during intestinal epithelial cell proliferation. Through the use of complementary GBP-1 overexpression and small interfering RNA-mediated knockdown studies, we now show that GBP-1 acts to inhibit pro-mitogenic ß-catenin/T cell factor (TCF) signaling. Interestingly, proinflammatory cytokine-induced GBP-1 was found to be a potent suppressor of ß-catenin protein levels and ß-catenin serine 552 phosphorylation. Neither glycogen synthase kinase 3ß nor proteasomal inhibition alleviated GBP-1-mediated suppression of cell proliferation or ß-catenin/TCF signaling, indicating a non-canonical mechanism of ß-catenin inhibition. Together, these data show that cytokine-induced GBP-1 retards cell proliferation by forming a negative feedback loop that suppresses ß-catenin/TCF signaling.


Subject(s)
Epithelial Cells/metabolism , GTP-Binding Proteins/genetics , Interferon-gamma/pharmacology , TCF Transcription Factors/antagonists & inhibitors , Tumor Necrosis Factor-alpha/pharmacology , beta Catenin/antagonists & inhibitors , Cell Line, Tumor , Cell Proliferation/drug effects , Epithelial Cells/drug effects , Epithelial Cells/immunology , Feedback, Physiological/drug effects , GTP-Binding Proteins/antagonists & inhibitors , GTP-Binding Proteins/immunology , Gene Expression/drug effects , Gene Expression/immunology , Glycogen Synthase Kinase 3/antagonists & inhibitors , Glycogen Synthase Kinase 3/genetics , Glycogen Synthase Kinase 3/immunology , Glycogen Synthase Kinase 3 beta , Humans , Intestinal Mucosa/drug effects , Intestinal Mucosa/immunology , Intestinal Mucosa/metabolism , Phosphorylation , Proteasome Endopeptidase Complex/genetics , Proteasome Endopeptidase Complex/immunology , Protein Kinase Inhibitors/pharmacology , RNA, Small Interfering/genetics , Serine/metabolism , Signal Transduction/drug effects , TCF Transcription Factors/genetics , TCF Transcription Factors/immunology , beta Catenin/genetics , beta Catenin/immunology
3.
J Insect Sci ; 2: 5, 2002.
Article in English | MEDLINE | ID: mdl-15455039

ABSTRACT

We present evidence for two behaviors influenced by intact, vegetative plant odor - upwind flight and abdomen curling - in female Manduca sexta and demonstrate the influence of the age and mating status of the moths on these behaviors. We compared the behavioral responses of laboratory-reared M. sexta. of discrete ages and physiological states (2,3, and 4 day old for virgin; 2 and 3 day old for mated) as individual moths flew upwind in a flight tunnel to a source of hostplant volatiles. We monitored odor-modulated flight and abdomen curling in the presence of volatiles released by potted hostplants. Mated 3 day old females exhibited the highest incidence of odor-modulated flight and abdomen curling. Similarly, as virgin moths aged, a greater percentage of the individuals displayed odor-modulated flight patterns and abdomen curling. In contrast, younger virgin moths exhibited high levels of abdomen curling only after contact with the plant.


Subject(s)
Manduca/physiology , Odorants , Sexual Behavior, Animal/physiology , Solanum lycopersicum/chemistry , Abdomen/physiology , Age Factors , Animals , Female , Flight, Animal/physiology , Manduca/drug effects , Oviposition/physiology , Sexual Behavior, Animal/drug effects , Wind
4.
J Biol Chem ; 275(43): 33836-43, 2000 Oct 27.
Article in English | MEDLINE | ID: mdl-10942774

ABSTRACT

The role and control of the four rapamycin-sensitive phosphorylation sites that govern the association of PHAS-I with the mRNA cap-binding protein, eukaryotic initiation factor 4E (eIF4E), were investigated by using newly developed phospho-specific antibodies. Thr(P)-36/45 antibodies reacted with all three forms of PHAS-I that were resolved when cell extracts were subjected to SDS-polyacrylamide gel electrophoresis. Thr(P)-69 antibodies bound the forms of intermediate and lowest mobility, and Ser(P)-64 antibodies reacted only with the lowest mobility form. A portion of PHAS-I that copurified with eIF4E reacted with Thr(P)-36/45 and Thr(P)-69 antibodies but not with Ser(P)-64 antibodies. Insulin and/or amino acids increased, and rapamycin decreased, the reactivity of all three antibodies with PHAS-I in both HEK293 cells and 3T3-L1 adipocytes. Immunoprecipitated epitope-tagged mammalian target of rapamycin (mTOR) phosphorylated Thr-36/45. mTOR also phosphorylated Thr-69 and Ser-64 but only when purified immune complexes were incubated with the activating antibody, mTAb1. Interestingly, the phosphorylation of Thr-69 and Ser-64 was much more sensitive to inhibition by rapamycin-FKBP12 than the phosphorylation of Thr-36/45, and the phosphorylation of Ser-64 by mTOR was facilitated by phosphorylation of Thr-36, Thr-45, and Thr-69. In these respects the phosphorylation of PHAS-I by mTOR in vitro resembles the ordered phosphorylation of PHAS-I in cells.


Subject(s)
Antibodies/immunology , Carrier Proteins , Phosphoproteins/metabolism , Phosphotransferases (Alcohol Group Acceptor)/physiology , Protein Kinases , Sirolimus/pharmacology , Adaptor Proteins, Signal Transducing , Amino Acid Sequence , Amino Acids/pharmacology , Antibody Specificity , Cell Cycle Proteins , Cells, Cultured , Humans , Insulin/pharmacology , Molecular Sequence Data , Phosphoproteins/immunology , Phosphorylation , TOR Serine-Threonine Kinases , Tacrolimus Binding Protein 1A/pharmacology
SELECTION OF CITATIONS
SEARCH DETAIL
...