Dexamethasone and IL-10 stimulate glucocorticoid-induced leucine zipper synthesis by human mast cells.

International audienceBACKGROUND: Glucocorticoids (GCs) decrease tissue mast cell (MC) number and prevent their activation via their high-affinity IgE receptor. Glucocorticoid-induced leucine zipper (GILZ) is one of the GC-induced genes, which inhibits the functions of the transcriptional activators AP-1 and NF-kappaB. GILZ appears to be a critical actor in the anti-inflammatory and immunosuppressive effects of GCs in human T lymphocytes, macrophages and dendritic cells. AIMS OF THE STUDY: We investigated whether GILZ was produced by human MCs and whether GILZ synthesis was stimulated by GCs. We also investigated whether GILZ production was modulated by (i) IL-10, because of its common immunosuppressive properties with GCs, (ii) histamine because of its pro-inflammatory properties and (iii) IL-4 and IL-5 because of their ability to favour MC survival and proliferation with SCF. METHODS: The human MC lines HMC-1 5C6 and LAD-2, and cord blood-derived MCs (CB-MCs) were cultured alone or in the presence of GCs, IL-10, histamine, IL-4 or IL-5. The expression of GILZ was evaluated by using RT-PCR, Western blotting or immunocytochemistry. RESULTS: We found that human MC lines and CB-MCs constitutively produce GILZ. We also show that GCs and IL-10 stimulate GILZ production by human MCs. Our present results indicate that histamine, IL-4 and IL-5 alone or in combination with SCF do not downregulate GILZ production by MCs. CONCLUSIONS: These results show that GCs and IL-10 stimulate GILZ production by human MCs. As GILZ mediates anti-inflammatory effects of GCs in immune cells, we speculate that GILZ could account for the deactivation of MCs by GCs and IL-10

The route to the development of basal stem rot resistance in oil palm (Elaeis guineensis) via the discovery of lignin degradation process in the pathogen Ganoderma boninense

International audienceAlthough the oil palm (Elaeis guineensis) is the oil crop bearing the highest oil yield ha(-1) in South-East Asia, it is facing a deadly disease, the basal stem rot (BSR) which is caused by Ganoderma boninense a fungus found commonly in the soil and air. The actual mode of infection by G. boninense still remains unclear. Meanwhile, some suspected cases of BSR can result from root infection, presumably following root contact with soil inoculum or other infected roots. Hence, oil palm plantations are suffering significant loss of palms at the early stages, thus directly reducing their potential oil yield. In the present study, we selected 3 isolates of G. boninense with various degree of pathogenicity (low, medium and high) which were identified through nursery trials and we cultured these isolates on two different media (carbon rich culture and carbon rich culture incorporating oil palm saw dust). The purpose of culturing isolates in the latter medium is to mimic the presence of the host tissue as compared to the former which was used as a control. Transcriptome sequencing was conducted via an Illumina platform and we investigated the expression profiles exhibited by the 3 G. boninense isolates grown under different media. We hypothesized that cell wall degradation was one of the possible modes of infection by the pathogen, hence, transcripts involved in lignin degradation process - and particularly those associated to laccase genes - were studied in detail. Concurrently, a separate analysis (not reported here) identified 33 laccase genes based on our de novo G. boninense genome assembly. All these laccase genes (de novo) contain the laccase specific four domain sequence signature encompassing cysteine and histidine residues which are involved in copper binding. Through transcriptomic analyses, in which isolates are compared under different conditions, there is no significant gene transcript detected for the isolate showing the weakest pathogenicity. Forty-five transcripts were found to be up-regulated in the G. boninense isolate with medium pathogenicity. In the most pathogenic isolate we found 409 unique transcripts which were down-regulated and 376 unique transcripts which were up-regulated and one laccase-related transcript. As we investigated further for the isolates (between medium and most pathogenic) cultivated on carbon medium supplemented with oil palm saw dust, we found that 6,551 transcripts were up-regulated (7 transcripts were found to be associated with laccase) as compared to 6,964 transcripts which were down-regulated, of which 18 transcripts were differentially expressed between two isolates cultivated on carbon medium supplemented with oil palm saw dust

Role of the chemokine stromal cell-derived factor 1 in autoantibody production and nephritis in murine lupus.

International audienceIn normal mice, stromal cell-derived factor 1 (SDF-1/CXCL12) promotes the migration, proliferation, and survival of peritoneal B1a (PerB1a) lymphocytes. Because these cells express a self-reactive repertoire and are expanded in New Zealand Black/New Zealand White (NZB/W) mice, we tested their response to SDF-1 in such mice. PerB1a lymphocytes from NZB/W mice were exceedingly sensitive to SDF-1. This greater sensitivity was due to the NZB genetic background, it was not observed for other B lymphocyte subpopulations, and it was modulated by IL-10. SDF-1 was produced constitutively in the peritoneal cavity and in the spleen. It was also produced by podocytes in the glomeruli of NZB/W mice with nephritis. The administration of antagonists of either SDF-1 or IL-10 early in life prevented the development of autoantibodies, nephritis, and death in NZB/W mice. Initiation of anti-SDF-1 mAb treatment later in life, in mice with established nephritis, inhibited autoantibody production, abolished proteinuria and Ig deposition, and reversed morphological changes in the kidneys. This treatment also counteracted B1a lymphocyte expansion and T lymphocyte activation. Therefore, PerB1a lymphocytes are abnormally sensitive to the combined action of SDF-1 and IL-10 in NZB/W mice, and SDF-1 is key in the development of autoimmunity in this murine model of lupus

The ETHICA study (part I): elderly's thoughts about intensive care unit admission for life-sustaining treatments.

PURPOSE: To assess preferences among individuals aged >/=80 years for a future hypothetical critical illness requiring life-sustaining treatments. METHODS: Observational cohort study of consecutive community-dwelling elderly individuals previously hospitalised in medical or surgical wards and of volunteers residing in nursing homes or assisted-living facilities. The participants were interviewed at their place of residence after viewing films of scenarios involving the use of non-invasive mechanical ventilation (NIV), invasive mechanical ventilation (IMV), and renal replacement therapy after a period of invasive mechanical ventilation (RRT after IMV). Demographic, clinical, and quality-of-life data were collected. Participants chose among four responses regarding life-sustaining treatments: consent, refusal, no opinion, and letting the physicians decide. RESULTS: The sample size was 115 and the response rate 87 %. Mean participant age was 84.8 +/- 3.5 years, 68 % were female, and 81 % and 71 % were independent for instrumental activities and activities of daily living, respectively. Refusal rates among the elderly were 27 % for NIV, 43 % for IMV, and 63 % for RRT (after IMV). Demographic characteristics associated with refusal were married status for NIV [relative risk (RR), 2.9; 95 % confidence interval (95 %CI), 1.5-5.8; p = 0.002] and female gender for IMV (RR, 2.4; 95 %CI, 1.2-4.5; p = 0.01) and RRT (after IMV) (RR, 2.7; 95 %CI, 1.4-5.2; p = 0.004). Quality of life was associated with choices regarding all three life-sustaining treatments. CONCLUSIONS: Independent elderly individuals were rather reluctant to accept life-sustaining treatments, especially IMV and RRT (after IMV). Their quality of life was among the determinants of their choices