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Laura C. Burzynski Melanie Humphry Martin R. Bennett Murray C. H. Clarke 《The Journal of biological chemistry》2015,290(41):25188-25196
Inflammation is a key instigator of the immune responses that drive atherosclerosis and allograft rejection. IL-1α, a powerful cytokine that activates both innate and adaptive immunity, induces vessel inflammation after release from necrotic vascular smooth muscle cells (VSMCs). Similarly, IL-1α released from endothelial cells (ECs) damaged during transplant drives allograft rejection. However, IL-1α requires cleavage for full cytokine activity, and what controls cleavage in necrotic ECs is currently unknown. We find that ECs have very low levels of IL-1α activity upon necrosis. However, TNFα or IL-1 induces significant levels of active IL-1α in EC necrotic lysates without alteration in protein levels. Increased activity requires cleavage of IL-1α by calpain to the more active mature form. Immunofluorescence and proximity ligation assays show that IL-1α associates with interleukin-1 receptor-2, and this association is decreased by TNFα or IL-1 and requires caspase activity. Thus, TNFα or IL-1 treatment of ECs leads to caspase proteolytic activity that cleaves interleukin-1 receptor-2, allowing IL-1α dissociation and subsequent processing by calpain. Importantly, ECs could be primed by IL-1α from adjacent damaged VSMCs, and necrotic ECs could activate neighboring normal ECs and VSMCs, causing them to release inflammatory cytokines and up-regulate adhesion molecules, thus amplifying inflammation. These data unravel the molecular mechanisms and interplay between damaged ECs and VSMCs that lead to activation of IL-1α and, thus, initiation of adaptive responses that cause graft rejection. 相似文献
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Mohamed M. Eid Samy I. El-Kowrany Ahmad A. Othman Dina I. El Gendy Eman M. Saied 《The Korean journal of parasitology》2015,53(1):51-58
Toxocariasis is a soil-transmitted helminthozoonosis due to infection of humans by larvae of Toxocara canis. The disease could produce cognitive and behavioral disturbances especially in children. Meanwhile, in our modern era, the incidence of immunosuppression has been progressively increasing due to increased incidence of malignancy as well as increased use of immunosuppressive agents. The present study aimed at comparing some of the pathological and immunological alterations in the brain of normal and immunosuppressed mice experimentally infected with T. canis. Therefore, 180 Swiss albino mice were divided into 4 groups including normal (control) group, immunocompetent T. canis-infected group, immunosuppressed group (control), and immunosuppressed infected group. Infected mice were subjected to larval counts in the brain, and the brains from all mice were assessed for histopathological changes, astrogliosis, and IL-5 mRNA expression levels in brain tissues. The results showed that under immunosuppression, there were significant increase in brain larval counts, significant enhancement of reactive gliosis, and significant reduction in IL-5 mRNA expression. All these changes were maximal in the chronic stage of infection. In conclusion, the immunopathological alterations in the brains of infected animals were progressive over time, and were exaggerated under the effect of immunosuppression as did the intensity of cerebral infection. 相似文献
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Adiponectin promotes human jaw bone marrow mesenchymal stem cell chemotaxis via CXCL1 and CXCL8 下载免费PDF全文
《Journal of cellular and molecular medicine》2017,21(7):1411-1419
Adiponectin (APN) is known to promote the osteogenic differentiation of human jaw bone marrow mesenchymal stem cells (h‐JBMMSCs). However, the underlying mechanism has not been fully elucidated. Previously, we showed that APN could promote h‐JBMMSC osteogenesis via APPL1‐p38 by up‐regulating osteogenesis‐related genes. Here, we aimed to determine whether APN could promote h‐JBMMSC chemotaxis through CXCL1/CXCL8. The CCK‐8, wound healing and transwell assays were used to evaluate the proliferation, migration and chemotaxis of h‐JBMMSCs with or without APN treatment. Chemotaxis‐related genes were screened using RNA‐seq, and the results were validated using real‐time PCR and ELISA. We also performed Western blot using the AMPK inhibitor, WZ4003, and the p38 MAPK inhibitor, SB203580, to identify the signalling pathway involved. We found that APN could promote h‐JBMMSC chemotaxis in the co‐culture transwell system. CXCL1 and CXCL8 were screened and confirmed as the up‐regulated target genes. The APN‐induced CXCL1/8 up‐regulation to promote chemotaxis could be blocked by CXCR2 inhibitor SB225002. Western blot revealed that the phosphorylation of AMPK and p38 MAPK increased in a time‐dependent manner with APN treatment. Additionally, WZ4003 and SB203580 could suppress the APN‐induced overexpression of CXCL1 and CXCL8. The results of the transwell chemotaxis assay also supported the above results. Our data suggest that APN can promote h‐JBMMSC chemotaxis by up‐regulating CXCL1 and CXCL8. 相似文献
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Kenji Tsuji Shinji KitamuraHirofumi Makino 《Biochemical and biophysical research communications》2014
The kidneys are exposed to hypoxic conditions during development. Hypoxia-inducible factor (HIF), an important mediator of the response to hypoxia, is believed to have an important role in development. However, the relationship between HIF and branching morphogenesis has not been elucidated clearly. 相似文献
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Nutrients are assimilated efficiently by Lymantria dispar caterpillars from the mature leaves of trees in the Salicaceae 下载免费PDF全文
Raymond V. Barbehenn Jennifer Knister Frank Marsik Chelsea Jahant‐Miller William Nham 《Physiological Entomology》2015,40(1):72-81
The efficient aquisition of nutrients from leaves by insect herbivores increases their nutrient assimilation rates and overall fitness. Caterpillars of the gypsy moth (Lymantria dispar L.) have high protein assimilation efficiencies (PAE) from the immature leaves of trees such as red oak (Quercus rubra) and sugar maple (Acer saccharum) (71–81%) but significantly lower PAE from their mature leaves (45–52%). By contrast to this pattern, both PAE and carbohydrate assimilation efficiencies (CAE) remain high for L. dispar larvae on the mature leaves of poplar (Populus alba × Populus tremula) grown in greenhouse conditions. The present study tests two alternative hypotheses: (i) outdoor environmental stresses cause decreased nutrient assimilation efficiencies from mature poplar leaves and (ii) nutrients in the mature leaves of trees in the poplar family (Salicaceae) remain readily available for L. dispar larvae. When poplar trees are grown in ambient outdoor conditions, PAE and CAE remain high (approximately 75% and 78%, respectively) in L. dispar larvae, in contrast to the first hypothesis. When larvae feed on the mature leaves of species in the Salicaceae [aspen (Populus tremuloides), cottonwood (Populus deltoides), willow (Salix nigra) and poplar], PAE and CAE also remain high (68–76% and 72–92%, respectively), consistent with the second hypothesis. Larval growth rates are strongly associated with protein assimilation rates, and more strongly associated with protein assimilation rates than with carbohydrate assimilation rates. It is concluded that tree species in the Salicaceae are relatively high‐quality host plants for L. dispar larvae, in part, because nutrients in their mature leaves remain readily available. 相似文献
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Nevena Cvetesic Mirna Bilus Ita Gruic-Sovulj 《The Journal of biological chemistry》2015,290(22):13981-13991
Aminoacyl-tRNA synthetases catalyze ATP-dependent covalent coupling of cognate amino acids and tRNAs for ribosomal protein synthesis. Escherichia coli isoleucyl-tRNA synthetase (IleRS) exploits both the tRNA-dependent pre- and post-transfer editing pathways to minimize errors in translation. However, the molecular mechanisms by which tRNAIle organizes the synthetic site to enhance pre-transfer editing, an idiosyncratic feature of IleRS, remains elusive. Here we show that tRNAIle affects both the synthetic and editing reactions localized within the IleRS synthetic site. In a complex with cognate tRNA, IleRS exhibits a 10-fold faster aminoacyl-AMP hydrolysis and a 10-fold drop in amino acid affinity relative to the free enzyme. Remarkably, the specificity against non-cognate valine was not improved by the presence of tRNA in either of these processes. Instead, amino acid specificity is determined by the protein component per se, whereas the tRNA promotes catalytic performance of the synthetic site, bringing about less error-prone and kinetically optimized isoleucyl-tRNAIle synthesis under cellular conditions. Finally, the extent to which tRNAIle modulates activation and pre-transfer editing is independent of the intactness of its 3′-end. This finding decouples aminoacylation and pre-transfer editing within the IleRS synthetic site and further demonstrates that the A76 hydroxyl groups participate in post-transfer editing only. The data are consistent with a model whereby the 3′-end of the tRNA remains free to sample different positions within the IleRS·tRNA complex, whereas the fine-tuning of the synthetic site is attained via conformational rearrangement of the enzyme through the interactions with the remaining parts of the tRNA body. 相似文献