1,721,066 research outputs found
Integrin-mediated stimulation of tyrosine phosphorylation in lymphoid cells.
No full text[No abstract available
Uterine NK cell development, migration and function
No full textUterine natural killer (uNK) cells represent the predominant lymphocytes in the uterus during early pregnancy and in the secretory phase of the menstrual cycle. They are CD56(high)CD16(-) and have low cytotoxicity, but constitutively secrete a number of cytokines, chemokines and angiogenic molecules. uNK cells differ from CD56(high) blood NK cells in several ways, including the killer cell immunoglobulin-like receptor repertoire and expression of some genes induced by hormone environment. uNK cells may arise by in-utero proliferation and differentiation of NK cell progenitors under the control of the sex steroid hormones and/or cytokines, such as interleukin-15, and/or be recruited from CD56(+) blood NK cells that would undergo tissue-specific differentiation in the uterine microenvironment. There is evidence showing that uNK cells display a different pattern of chemokine receptors and adhesion molecules, thus leading to a different migratory response. It has not yet been fully defined which uNK cell function(s) are critical for successful pregnancy. The close encirclement of spiral arteries by NK cells, together with their ability to produce angiogenic factors, suggests that they might influence mucosal vascularization. Their proximity to the extravillous trophoblast supports the idea that uNK cells could recognize these cells as fetal, and regulate their invasion during placentation
Negative regulation of innate lymphoid cell responses in inflammation and cancer
No full textThe immune system employs an array of effector cells to ensure tissue homeostasis and protection against pathogens. Lymphocytes belonging to both the adaptive and innate branches share several functions, comprising the ability to directly kill stressed or transformed cells, and to provide helper responses through specific production of cytokines. These properties are regulated by distinct sets of soluble molecules, receptors, and intracellular factors, which altogether tune the functional output of effector lymphocytes and their final activation state. In contrast to adaptive T cells, innate lymphoid cells (ILCs) do not require antigen receptors and are characterized for their ability to provide rapid immune responses. While the factors underlying functional diversification and the main principles leading to ILC activation have been dissected, our understanding of the mechanisms underlying termination of ILC effector functions is still in its infancy. Herein, we discuss the recent findings describing how ILC responses are turned off in the context of inflammation and cancer
Tissue distribution, urinary, fecal and biliary excretion of 14C bendazac L-lysine salt in rats.
No full textThe distribution of bendazac in the plasma and some rat tissues was studied after single oral administration of 14C bendazac L-lysine salt. The drug is distributed in varying amounts in the liver, kidneys, spleen, muscle, plasma and lens. In these tissues, the drug kinetics is similar, except for the lens where elimination of the drug is slower. More than 80% of the radioactivity administered is excreted through the urine and feces. Fecal excretion is due to the high biliary excretion.The distribution of bendazac in the plasma and some rat tissues was studied after single oral administration of 14C bendazac L-lysine salt. The drug is distributed in varying amounts in the liver, kidneys, spleen, muscle, plasma and lens. In these tissues, the drug kinetics is similar, except for the lens where elimination of the drug is slower. More than 80% of the radioactivity administered is excreted through the urine and feces. Fecal excretion is due to the high biliary excretion
Beta 1-integrin expression and function in human bladder cancer cells: modulation by TNF-alpha.
No full textCytofluorimetric and biochemical analysis ill two different grade human bladder cancer cell lines showed that G3 EJ cells exhibited higher levels of alpha 5 beta 1 and alpha 6 beta 1 heterodimers, and the G2 RT112 cell line higher levels of alpha 2 beta 1. Alpha6/beta4 receptor was detected only in RT112 cells. Adhesion assays with extracellular matrix proteins indicated that both cells bound to fibronectin, laminin and collagen I, the adhesive properties bring related to the integrin profile. Inhibition tests revealed that alpha 5 beta 1 mediated adhesion to fibronectin, alpha 3 beta 1 and alpha 6 beta 1 to laminin, and that alpha 2 beta 1 was the main mediator of adhesion to collagen I in both cell lines. In EJ but not in RT112 cells, tumor necrosis factor-alpha induced the upregulation of alpha 2, which mediated increased adhesion to collagen I. The different effects of TNF alpha on the two cell lines were not attributable to differences in tumor necrosis factor responsiveness, as both cells expressed comparable levels of tumor necrosis factor receptor-1 and the tumor necrosis factor-inducible intercellular adhesion molecule-1
Role of the alpha 5 beta 1 integrin receptor in the proliferative response of quiescent human melanoma cells to fibronectin.
No full textThe possible mitogenic activity of fibronectin (FN) in human primary and metastatic melanoma lines and clones and the involvement of integrins in mediating this effect were evaluated. Quiescent human melanoma cells cultured in serum-free medium proliferated in a dose- and time-dependent fashion to immobilized FN as indicated by [H-3]thymidine incorporation, increment of cell number, and cell cycle analysis. This response to FN was observed with tumor clones isolated from a subcutaneous metastasis and with primary or metastatic melanomas from different patients, but only when tumor cells expressed the alpha-5 subunit of the FN receptor (i.e., VLA-5). Proliferation to FN by a primary tumor (Me4405) expressing all FN receptors and by a tumor clone (2/60) lacking only the alpha-4 subunit was inhibited by monoclonal antibodies to the alpha-5 and beta-1 but not by monoclonal antibodies to other subunits of FN receptors. Mapping of FN regions responsible for the proliferative signal was performed by stimulating melanoma cells with different FN proteolytic fragments and indicated that a significant mitogenic signal was provided by the M(r) 120,000 alpha-chymotrypsin fragment containing the Arg-Gly-Asp sequence. The proliferation of melanoma cells to FN and to FN fragments was also significantly inhibited by peptides containing the Arg-Gly-Asp sequence. These data indicate that FN can stimulate the proliferation of quiescent melanoma cells and that integrins as alpha-5-beta-1 are involved in the response of tumor cells to this extracellular matrix protein
Reduction of invasive potential in K-ras-transformed thyroid cells by restoring of TGF-beta pathway
No full textTransforming Growth Factor-beta1 (TGF-beta 1) is a multifunctional cytokine that regulates a number of cellular processes such as cell growth, differentiation, plasticity, cell motility, adhesiveness, embryogenesis, development and apoptosis through binding to TGF-beta receptors. We have previously demonstrated that K-ras-transformed rat thyroid cells, K10, are resistant to the growth inhibitory action of TGF-beta 1, because they show a decreased expression of type II receptor (T beta RII). Clones obtained transfecting T beta RII, partially revert their malignant phenotype, showing a reduction in the anchorage-dependent and -independent cell growth and a statistically significant decrease in tumourigenicity with respect to the highly malignant parental cells, both in spontaneous and artificial metastases, when transplanted in athymic nude mice. The purpose of the present work is to elucidate the molecular events involved in the modulation of the tumourigenic potential of K-ras-transformed rat thyroid cells overexpressing T beta RII. Our data demonstrate that the T beta RII overexpressed in K-ras-transformed thyroid cell clones is a functional receptor and is essential to restore in these cells behaviour similar to that of control cells. The T beta RII overexpression is responsible for a strong reduction of adhesive and migratory behaviour of highly malignant K-ras-transformed thyroid cells. These results suggest that the restore of a functional TGF-beta receptor in these cells may be useful for the limitation of tumour spread and dissemination
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