XBP1 governs late events in plasma cell differentiation and is not required for antigen-specific memory B cell development

The unfolded protein response (UPR) is a stress response pathway that is driven by the increased load of unfolded proteins in the endoplasmic reticulum of highly secretory cells such as plasma cells (PCs). X box binding protein 1 (XBP1) is a transcription factor that mediates one branch of the UPR and is crucial for the development of antibody-secreting PCs. PCs represent only one class of terminally differentiated B cells, however, and little is known about the role for XBP1 in the other class: memory B cells. We have developed an XBP1fl/fl CD19+/cre conditional knockout (XBP1CD19) mouse to build upon our current understanding of the function of XBP1 in PC differentiation as well as to explore the role of XBP1 in memory cell development. Using this model, we show that XBP1CD19 mice are protected from disease in an autoantibody-mediated mouse lupus model. We also identify a novel developmental stage at which B cells express the traditional PC marker CD138 (syndecan-1) but have yet to undergo XBP1-dependent functional and morphological differentiation into antibody-secreting cells. Finally, we show that memory B cells develop normally in XBP1CD19 mice, demonstrating that XBP1-mediated functions occur independently of any memory cell lineage commitment

Proline-rich antimicrobial peptide, PR-39 gene transduction altered invasive activity and actin structure in human hepatocellular carcinoma cells

PR-39 is an endogenous proline-rich antimicrobial peptide which induces the synthesis of syndecan-1, a transmembrane heparan sulphate proteoglycan involved in cell-to-matrix interactions and wound healing. Previously, we revealed that the expression of syndecan-1 was reduced in human hepatocellular carcinomas with high metastatic potential and speculated that syndecan-1 played an important role in inhibition of invasion and metastasis. It is assumed that a modification of this process with PR-39 and syndecan-1 may result in a new strategy by which it can inhibit the invasion and metastasis. Therefore, we transduced a gene of PR-39 into human hepatocellular carcinoma cell line HLF, which shows a low expression of syndecan-1 and a high in vitro invasive activity, and examined whether this procedure could reduce the invasive activity of tumour cells. In two transfectants with PR-39 gene, the syndecan-1 expression was induced and the invasive activity in type I collagen-coated chamber was inhibited. Moreover, these transfectants showed the suppression of motile activity assayed by phagokinetic tracks in addition to the disorganization of actin filaments observed by a confocal imaging system. In contrast, five transfectants with syndecan-1 gene in the HLF cells revealed suppression of invasive activity but did not alter the motile activity and actin structures of the cell. These results suggest that PR-39 has functions involved in the suppression of motile activity and alteration of actin structure on human hepatocellular carcinoma cells in addition to the suppression of invasive activity which might result from the induction of syndecan-1 expression. © 1999 Cancer Research Campaig

Effects of green tea polyphenol on methylation status of RECK gene and cancer cell invasion in oral squamous cell carcinoma cells

RECK is a novel tumour suppressor gene that negatively regulates matrix metalloproteinases (MMPs) and inhibits tumour invasion, angiogenesis and metastasis. In the present study, we investigated the effects of epigallocatechin-3-gallate (EGCG), a major polyphenol in green tea, on the methylation status of the RECK gene and cancer invasion in oral squamous cell carcinoma cell lines. Our results showed that treatment of oral cancer cells with EGCG partially reversed the hypermethylation status of the RECK gene and significantly enhanced the expression level of RECK mRNA. Inhibition of MMP-2 and MMP-9 levels was also observed in these cells after treatment with EGCG. Interestingly, EGCG significantly suppressed cancer cell-invasive ability by decreasing the number of invasive foci (P<0.0001) as well as invasion depth (P<0.005) in three-dimensional collagen invasion model. Although further investigation is required to assess the extent of contribution of RECK on MMPs to the suppression of invasive behaviour, these results support the conclusion that EGCG plays a key role in suppressing cell invasion through multiple mechanisms, possibly by demethylation effect on MMP inhibitors such as RECK

Effects of land use intensity on the full greenhouse gas balance in an Atlantic peat bog

Wetlands can either be net sinks or net sources of greenhouse gases (GHGs), depending on the mean annual water level and other factors like average annual temperature, vegetation development, and land use. Whereas drained and agriculturally used peatlands tend to be carbon dioxide (CO&lt;sub&gt;2&lt;/sub&gt;) and nitrous oxide (N&lt;sub&gt;2&lt;/sub&gt;O) sources but methane (CH&lt;sub&gt;4&lt;/sub&gt;) sinks, restored (i.e. rewetted) peatlands rather incorporate CO&lt;sub&gt;2&lt;/sub&gt;, tend to be N&lt;sub&gt;2&lt;/sub&gt;O neutral and release CH&lt;sub&gt;4&lt;/sub&gt;. One of the aims of peatland restoration is to decrease their global warming potential (GWP) by reducing GHG emissions. &lt;br&gt;&lt;br&gt; We estimated the greenhouse gas exchange of a peat bog restoration sequence over a period of 2 yr (1 July 2007–30 June 2009) in an Atlantic raised bog in northwest Germany. We set up three study sites representing different land use intensities: intensive grassland (deeply drained, mineral fertilizer, cattle manure and 4–5 cuts per year); extensive grassland (rewetted, no fertilizer or manure, up to 1 cutting per year); near-natural peat bog (almost no anthropogenic influence). Daily and annual greenhouse gas exchange was estimated based on closed-chamber measurements. CH&lt;sub&gt;4&lt;/sub&gt; and N&lt;sub&gt;2&lt;/sub&gt;O fluxes were recorded bi-weekly, and net ecosystem exchange (NEE) measurements were carried out every 3–4 weeks. Annual sums of CH&lt;sub&gt;4&lt;/sub&gt; and N&lt;sub&gt;2&lt;/sub&gt;O fluxes were estimated by linear interpolation while NEE was modelled. &lt;br&gt;&lt;br&gt; Regarding GWP, the intensive grassland site emitted 564 ± 255 g CO&lt;sub&gt;2&lt;/sub&gt;–C equivalents m&lt;sup&gt;−2&lt;/sup&gt; yr&lt;sup&gt;−1&lt;/sup&gt; and 850 ± 238 g CO&lt;sub&gt;2&lt;/sub&gt;–C equivalents m&lt;sup&gt;−2&lt;/sup&gt; yr&lt;sup&gt;−1&lt;/sup&gt; in the first (2007/2008) and the second (2008/2009) measuring year, respectively. The GWP of the extensive grassland amounted to −129 ± 231 g CO&lt;sub&gt;2&lt;/sub&gt;–C equivalents m&lt;sup&gt;−2&lt;/sup&gt; yr&lt;sup&gt;−1&lt;/sup&gt; and 94 ± 200 g CO&lt;sub&gt;2&lt;/sub&gt;–C equivalents m&lt;sup&gt;−2&lt;/sup&gt; yr&lt;sup&gt;−1&lt;/sup&gt;, while it added up to 45 ± 117 g CO&lt;sub&gt;2&lt;/sub&gt;–C equivalents m&lt;sup&gt;−2&lt;/sup&gt; yr&lt;sup&gt;−1&lt;/sup&gt; and −101 ± 93 g CO&lt;sub&gt;2&lt;/sub&gt;–C equivalents m&lt;sup&gt;−2&lt;/sup&gt; yr&lt;sup&gt;−1&lt;/sup&gt; in 2007/08 and 2008/09 for the near-natural site. In contrast, in calendar year 2008 GWP aggregated to 441 ± 201 g CO&lt;sub&gt;2&lt;/sub&gt;–C equivalents m&lt;sup&gt;−2&lt;/sup&gt; yr&lt;sup&gt;−1&lt;/sup&gt;, 14 ± 162 g CO&lt;sub&gt;2&lt;/sub&gt;–C equivalents m&lt;sup&gt;−2&lt;/sup&gt; yr&lt;sup&gt;−1&lt;/sup&gt; and 31 ± 75 g CO&lt;sub&gt;2&lt;/sub&gt;–C equivalents m&lt;sup&gt;−2&lt;/sup&gt; yr&lt;sup&gt;−1&lt;/sup&gt; for the intensive grassland, extensive grassland, and near-natural site, respectively. &lt;br&gt;&lt;br&gt; Despite inter-annual variability, rewetting contributes considerably to mitigating GHG emission from formerly drained peatlands. Extensively used grassland on moderately drained peat approaches the carbon sequestration potential of near-natural sites, although it may oscillate between being a small sink and being a small source depending on inter-annual climatic variability