Interleukin 3 (IL-3) is required for the survival and proliferation of the FDCP-Mix 1 multipotent stem cell line. IL-3 or phorbol esters can rapidly translocate protein kinase C from a cytosolic to a membrane-bound form in these cells. Phorbol esters were able to partially replace the requirement of FDCP-Mix 1 cells for IL-3. Down-modulation of protein kinase C levels by chronic treatment with phorbol ester markedly reduced the ability of the cells to proliferate in response to either IL-3 or phorbol esters. These data indicate that IL-3 can activate protein kinase C, leading to the survival and proliferation of stem cells. Protein kinase C is activated conventionally by complexing with diacylglycerol which accumulates in the cell membrane after agonist-stimulated hydrolysis of phosphatidylinositol 4,5-bisphosphate [Ptdlns(4,5)P2].
Infection and injury of the gut are associated with cell damage and release of molecules such as extracellular adenosine 5′-triphosphate (ATP), which is recognised by the purinergic P2X7 receptor (P2X7R). P2X7R is widely expressed in the gut by antigen-presenting cells (APCs) and epithelial cells, but the role of the P2X7R on epithelial cells is poorly understood. We investigated P2X7R in intestinal epithelium in vitro and in vivo using two model infections, Toxoplasma gondii and Trichinella spiralis. Lipopolysaccharide and ATP treatment of intestinal epithelial cells and infection with T. gondii in vitro did not promote inflammasome-associated interleukin-1β (IL-1β) or IL-18 secretion, but promoted C–C motif chemokine ligand 5 (CCL5), tumour necrosis factor-α and IL-6 production that were significantly reduced when the P2X7R was blocked. Similarly, in vivo, infection with either T. spiralis or T. gondii induced rapid upregulation of epithelial CCL5 in wild-type (wild-type (WT)) mice that was significantly reduced in P2X7R−/− littermate controls. The effects of reduced epithelial CCL5 were assayed by investigating recruitment of dendritic cells (DCs) to the epithelium. Infection induced a rapid recruitment of CD11c+CD103+ DC subsets into the epithelial layer of WT mice but not P2X7R−/− mice. In vitro chemotaxis assays and bone marrow chimeras demonstrated the importance of epithelial P2X7R in DC recruitment. P2X7R signalling in epithelial cells mediates chemokine responses to promote initiation of host immunity to infection.
To investigate the relationship between inositol lipid hydrolysis and reactive oxygen-intermediate (ROI) production in macrophages we have examined the effect of platelet-activating factor (PAF) on normal bone marrow-derived macrophages. Addition of PAF to macrophages prelabelled with [3H]inositol caused a marked and rapid increase in [3H]inositol trisphosphate levels. Similarly when PAF was added to [3H]-glycerol prelabelled macrophages there was a rapid increase in 1,2-diacyl[3H]glycerol levels. These events preceded any increase in the rate of PAF-stimulated ROI production by a discernible period of several seconds. Increasing concentrations of PAF led to a markedly similar increase in both ROI production and [3H]inositol lipid hydrolysis suggesting that inositol lipid hydrolysis may lead to the generation of ROI in macrophages. Further evidence that this is the case came from experiments in which pretreatment of macrophages with phorbol esters was shown to inhibit both PAF-stimulated [3H]inositol phosphate production and ROI production to a markedly similar degree. Similarly pertussis toxin inhibited both PAF-stimulated ROI production and [3H]inositol phosphate production. Phorbol esters were shown to activate ROI production in normal bone marrow-derived macrophages whereas the Ca2+ ionophore, A23187, did not. These experiments suggest that PAF stimulates a pertussis toxin-sensitive activation of inositol lipid hydrolysis leading to the formation of inositol trisphosphate and diacylglycerol. The diacylglycerol formed can then activate protein kinase C leading to the stimulation of ROI production in normal bone marrow-derived macrophages.
This study provides a design diagram which involves a series of pragmatic strategies for ecological remediation and restoration of plain river networks in the Yangtze River Delta. The design diagram is composed of two stages: the first concerns the reduction of pollutants, including those from non-point sources, point sources, and river sediments; the second, the restoration of the biological habitat, including the riparian zone and aquatic habitat. A case study of Gehu Lake was used as an example for the implementation of the suggested design diagram, and further suggestions were provided for the improvement of remediation work in plain river network areas. This research provides valuable insights into the methods of ecological restoration, and demonstrates the potential for multidisciplinary collaboration to help improve the environmental health of plain river networks.
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