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1.
Paracoccidioides brasiliensis Interferes on Dendritic Cells Maturation by Inhibiting PGE2 Production
Reginaldo K. Fernandes Tatiana F. Bachiega Daniela R. Rodrigues Marjorie de A. Golim Luciane A. Dias-Melicio Helanderson de A. Balderramas Ramon Kaneno ?ngela M. V. C. Soares 《PloS one》2015,10(3)
Paracoccidioidomycosis (PCM) is a systemic mycosis, endemic in most Latin American countries, especially in Brazil, whose etiologic agent is the thermodimorphic fungus of the genus Paracoccidioides, comprising cryptic species of Paracoccidioides brasiliensis, S1, PS2, PS3 and Paracoccidioides lutzii. The mechanisms involved in the initial interaction of the fungus with cells of the innate immune response, as dendritic cells (DCs), deserve to be studied. Prostaglandins (PGs) are eicosanoids that play an important role in modulating functions of immune cells including DCs. Here we found that human immature DCs derived from the differentiation of monocytes cultured with GM-CSF and IL-4 release substantial concentrations of PGE2, which, however, were significantly inhibited after challenge with P. brasiliensis. In vitro blocking of pattern recognition receptors (PRRs) by monoclonal antibodies showed the involvement of mannose receptor (MR) in PGE2 inhibition by the fungus. In addition, phenotyping assays showed that after challenge with the fungus, DCs do not change their phenotype of immature cells to mature ones, as well as do not produce IL-12 p70 or adequate concentrations of TNF-α. Assays using exogenous PGE2 confirmed an association between PGE2 inhibition and failure of cells to phenotypically mature in response to P. brasiliensis. We conclude that a P. brasiliensis evasion mechanism exists associated to a dysregulation on DC maturation. These findings may provide novel information for the understanding of the complex interplay between the host and this fungus. 相似文献
2.
Theofilos Poutahidis Sean M. Kearney Tatiana Levkovich Peimin Qi Bernard J. Varian Jessica R. Lakritz Yassin M. Ibrahim Antonis Chatzigiagkos Eric J. Alm Susan E. Erdman 《PloS one》2013,8(10)
Wound healing capability is inextricably linked with diverse aspects of physical fitness ranging from recovery after minor injuries and surgery to diabetes and some types of cancer. Impact of the microbiome upon the mammalian wound healing process is poorly understood. We discover that supplementing the gut microbiome with lactic acid microbes in drinking water accelerates the wound-healing process to occur in half the time required for matched control animals. Further, we find that Lactobacillus reuteri enhances wound-healing properties through up-regulation of the neuropeptide hormone oxytocin, a factor integral in social bonding and reproduction, by a vagus nerve-mediated pathway. Bacteria-triggered oxytocin serves to activate host CD4+Foxp3+CD25+ immune T regulatory cells conveying transplantable wound healing capacity to naive Rag2-deficient animals. This study determined oxytocin to be a novel component of a multi-directional gut microbe-brain-immune axis, with wound-healing capability as a previously unrecognized output of this axis. We also provide experimental evidence to support long-standing medical traditions associating diet, social practices, and the immune system with efficient recovery after injury, sustained good health, and longevity. 相似文献
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Exogenous long-chain fatty acids are readily taken up by unstimulated lymphocytes derived from the thymus of calves or rabbits and esterified to complex lipids, primarily phospholipids and triacylglycerols. Compared to saturated fatty acids, unsaturated fatty acids are incorporated preferentially. Furthermore, unsaturated fatty acids are transferred from triacylglycerols to phospholipids. The transfer cannot be observed with palmitic acid. With regard to individual phospholipid species, oleic acid and linoleic acid are found primarily in phosphatidylcholine. Arachidonic acid, however, is transferred to phosphatidylethanolamine and phosphatidylinositol as well. This suggests an arachidonic-specific transfer between individual phospholipids. Stimulation of the cells with the mitogen concanavalin A results in an enhanced incorporation of the fatty acids and an enhanced transfer from triacylglycerols to phospholipids. Triacylglycerols may thus be regarded as a labile intracellular storage pool that may be activated upon mitogenic stimulation. 相似文献
5.
Tatiana V. Byzova Wes Kim Ronald J. Midura Edward F. Plow 《Experimental cell research》2000,254(2):299
αVβ3, a broadly distributed member of the integrin family of adhesion receptors, has been implicated in a variety of physiological and pathophysiological events, including control of bone density, angiogenesis, apoptosis, tumor growth, and metastasis. Recently, it has been shown that activation of αVβ3, its transition from a low- to a high-affinity/avidity state, influences its recognition of certain ligands. Bone sialoprotein (BSP) is recognized as an important ligand for αVβ3 in processes ranging from bone formation to the homing of metastatic tumor cells. Here, the influence of αVβ3 activation on the adhesion and migration of relevant cells to BSP has been examined. Stimulation of lymphoblastoid, osteoblastoid, and human umbilical vein endothelial cells (HUVEC) with PMA or Mn2+ markedly enhanced αVβ3-dependent adhesion to BSP. αVβ3-mediated migration of HUVEC or osteoblastic cells to BSP was substantially enhanced by stimulation, demonstrating that αVβ3 activation enhances both adhesive and migratory responses. However, adhesion and/or migration of certain tumor cell lines, including M21 melanoma and MDA MB435 and SKBR3 breast carcinoma cell lines, to BSP was constitutively high and was not augmented by αVβ3-activating stimuli. Inhibitors of the intracellular signaling molecules, phosphatidylinositol 3-kinase with wortmannin, hsp90-dependent kinases with geldanamycin, and calpain with calpeptin, but not MAPKK with PD98059, reduced the high spontaneous adhesion and migration of the M21 cells to BSP, consistent with the constitutive activation of the receptor on these tumor cells. These results indicate that the activation state of αVβ3 can regulate cell migration and adhesion to BSP and, by extension, to other ligands of this receptor. The constitutive activation of αVβ3 on neoplastic cells may contribute to tumor growth and metastatic potential. 相似文献
6.
Fluorescence polarization measurements with the probe 1,6-diphenyl-1,3,5-hexatriene (DPH) were performed to detect changes in the fluidity of plasma membranes from T-lymphocytes stimulated with mitogens. When the cells were incubated with succinyl-concanavalin A an increase in fluorescence polarization was observed. This, however, could be shown to be due to the interaction of the mitogen with the label DPH and did not reflect changes in the plasma membrane. In purified plasma membranes a decrease rather than an increase of fluorescence polarization was observed. 相似文献
7.
Regulation of prostaglandin synthesis by protein kinase C in mouse peritoneal macrophages. 总被引:2,自引:0,他引:2
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Resident mouse peritoneal macrophages synthesized and released prostaglandins (PGs) when challenged with 12-O-tetradecanoylphorbol 13-acetate (TPA) or 1,2-dioctanoyl-sn-glycerol (DiC8). Both stimuli were found to activate Ca2+/phospholipid-dependent protein kinase C (PKC). 1-(5-Isoquinolinesulphonyl)-2-methylpiperazine ('H-7') and D-sphingosine, known to inhibit PKC by different mechanisms, were able to decrease the PKC activity of macrophages in a dose-dependent manner. Addition of either PKC inhibitor decreased PG synthesis and also the release of arachidonic acid (AA) from phospholipids induced by TPA or DiC8. Simultaneously TPA or DiC8 also decreased incorporation of free AA into membrane phospholipids of macrophages. AA incorporation could be restored, however, by pretreatment with the PKC inhibitors. Our results demonstrate an involvement of PKC in the regulation of PG synthesis in mouse peritoneal macrophages and provide further evidence that reacylation of released fatty acids may be an important regulatory step. 相似文献
8.
Characterization of the interleukin-1-induced tyrosine phosphorylation of a 41-kDa plasma membrane protein of the human tumor cell line K 562 总被引:1,自引:0,他引:1
A 41-kDa protein, which was specifically phosphorylated upon incubation with natural purified murine interleukin 1, was recently identified by us [Martin, M., Lovett, D. H. and Resch, K. (1986) Immunobiology 171, 165-169] in highly purified plasma membranes from the human tumor cell line K 562. An in vitro assay was used to investigate and characterize the phosphorylation induced by interleukin 1, possibly involved in signal transduction and generation. Plasma membranes were incubated with radiolabeled ATP in the presence of purified natural murine interleukin 1, or recombinant human interleukin 1 alpha and the pattern of phosphoproteins was studied after separation by SDS/PAGE and subsequent autoradiography. A 41-kDa protein (pp41) was specifically phosphorylated on a tyrosine residue in the presence of interleukin 1 in a dose- and time-dependent manner. The protein showed a weak background phosphorylation in the absence of monokine. Phosphorylation took place very efficiently at 0 degrees C, whereas phosphatases were not active at that temperature. At 37 degrees C, a rapid dephosphorylation was observed which was inhibited specifically by Zn2+ and vanadate. The interleukin-1-specific induction of the phosphorylation could also be observed after detergent solubilization of the plasma membranes. Affinity labeling with an ATP analogue revealed an ATP-binding and cleaving site at 41 kDa. Interleukin 1 did not induce the phosphorylation of p41 in plasma membranes obtained from a subclone of K 562, which did not respond to interleukin 1 with growth inhibition, as was reported recently for the K 562 mother line [Lovett, D. H., Kozan, B., Hadam, M., Resch, K. and Gemsa, D. (1986) J. Immunol. 136, 340-347]. These data suggest that the interleukin-1 receptor is functionally linked to a protein-tyrosine kinase, which is implicated in its biological function. 相似文献
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10.
Treatment of human platelets by the purified late complement components C5b-9 results in a dose- and time-dependent release of prostaglandin E (PGE) and thromboxane B2 (TXB2). To study the mechanism underlying the complement-induced prostanoid synthesis, we examined whether C5b-9 affected the enzyme acyl-coA:lysolecithin acyltransferase (E.C.2.3.1.2.3) that catalyzes the reinsertion of liberated arachidonic acid, the precursor molecule of the prostanoids. With C5b-9 doses sufficient to induce prostanoid synthesis, the activity of lysolecithin acyltransferase, measured as conversion of lysophosphatidyl choline to phosphatidyl choline, was inhibited. For comparison, another channel-forming substance, nystatin, was studied. Nystatin had an effect similar to C5b-9: PGE and TXB2 release was stimulated, whereas acyltransferase activity was inhibited. These finding support the concept that inhibition of lysolecithin acyltransferase might be the prerequisite for prostanoid production. 相似文献