No abstract

The p38 mitogen-activated protein kinase (MAPK) signaling pathway can be activated by a variety of stress stimuli such as UV radiation and osmotic stress. The regulation and role of this pathway in death receptorinduced apoptosis remain unclear and may depend on the specific death receptor and cell type. Here we show that binding of Fas ligand to Fas activates p38 MAPK in CD8؉ T cells and that activation of this pathway is required for Fas-mediated CD8 ؉ T-cell death. Active p38 MAPK phosphorylates Bcl-x L and Bcl-2 and prevents the accumulation of these antiapoptotic molecules within the mitochondria. Consequently, a loss of mitochondrial membrane potential and the release of cytochrome c lead to the activation of caspase 9 and, subsequently, caspase 3. Therefore, the activation of p38 MAPK is a critical link between Fas and the mitochondrial death pathway and is required for the Fas-induced apoptosis of CD8 ؉ T cells.

In addition to immune cells, airway epithelial cells can contribute to and shape the immune response in the lung by secreting specific cytokines. IL-6 is a key factor in determining the effector fate of CD4(+) T cells. Here we show that under basal conditions, the IL-6 gene is already highly expressed in lung epithelial cells, but not in immune cells resident in the lung. However, upon exposure of the lungs to fungal allergens, the direct contact of β-glucans present in the fungus cell wall with lung epithelial cells is sufficient to trigger the rapid synthesis and secretion of IL-6 protein. This posttranscriptional regulation of IL-6 in response to fungal extracts is mediated by the p38 mitogen-activated protein kinase pathway. The inhalation of β-glucans with a nonallergenic antigen is sufficient to provide an adjuvant effect that leads to mucous hyperplasia in the airways. Thus, β-glucans may constitute a common determinant of the fungal and plant-derived allergens responsible for some of the pathological features in allergic asthma.

No abstract

Bluetongue virus (BTV) causes haemorrhagic disease in sheep and induces death in cultured mammalian cells. In the present study, BTV-induced apoptotic pathways in Vero cells were elucidated. Cells infected with BTV at 0.1 m.o.i underwent DNA fragmentation and membrane blebbing within 48 h postinfection. BTV-induced apoptosis was blocked by the pan-caspase inhibitor, z-VAD-FMK. Immuno-blotting using anti-caspase-8 and -9 antibodies detected the activation of the respective caspases. Flow cytometry analyses following 3, 3' dihexyloxacarbocyanine iodide staining revealed the loss of mitochondrial membrane potential. Our study confirms the involvement of both caspase-dependent extrinsic and intrinsic pathways of apoptosis in BTV-infected cells.

IP3 (inositol 1,4,5-trisphosphate) receptors (IP3Rs) regulate the release of Ca2+ from intracellular stores in response to IP3. Little is known about regulation of the expression of IP3Rs and their role during the activation of CD4 T cells. In this study we show that mouse naive CD4 T cells express IP3R1, IP3R2, and IP3R3, but that gene expression of IP3R3 primarily is down-regulated upon activation due to loss of the Ets-1 transcription factor. Down-regulation of IP3R expression in activated CD4 T cells is associated with the failure of TCR ligation to trigger Ca2+ release in these cells. We also show that down-regulation of specific IP3Rs in activated CD4 T cells correlates with the requirement of IP3R-mediated Ca2+ release only for the induction of, but not for the maintenance of, IL-2 and IFN-γ expression. Interestingly, while inhibition of IP3R function early during activation blocks IL-2 and IFN-γ production, it promotes the production of IL-17 by CD4 T cells. Thus, IP3Rs play a key role in the activation and differentiation of CD4 T cells. The immunosuppressive effect of pharmacological blockers of these receptors may be complicated by promoting the development of inflammatory CD4 T cells.

NKT cells are known to rapidly produce a large amount of cytokines upon activation. Although a number of signaling pathways that regulate the development of NKT cells have been identified, the signaling pathways involved in the regulation of NKT cell cytokine production remain unclear. Here we show that the p38 MAP kinase (MAPK) pathway is dispensable for the development of NKT cells. However, NKT cell cytokine production and NKT-mediated liver damage are highly dependent on activation of this pathway. p38 MAPK does not substantially affect cytokine gene expression in NKT cells, but it regulates the synthesis of cytokine through the Mnk/eIF4E pathway. Thus, in addition to gene expression, translational regulation by p38 MAPK could be a novel mechanism that contributes to the overall production of cytokine by NKT cells.

In this study, 108 P. multocida isolates recovered from various host animals such as cattle, buffalo, swine, poultry (chicken, duck, and emu) and rabbits were screened for carriage of 8 virulence associated genes. The results revealed some unique information on the prevalence of virulence associated genes among Indian isolates. With the exception of toxA gene, all other virulence associated genes were found to be regularly distributed among host species. Association study between capsule type and virulence genes suggested that pfhA, nanB, and nanH genes were regularly distributed among all serotypes with the exception of CapD, whereas toxA gene was found to be positively associated with CapD and CapA. The frequency of hgbA and nanH genes among swine isolates of Indian origin was found to be less in comparison to its equivalents around the globe. Interestingly, very high prevalence of tbpA gene was observed among poultry, swine, and rabbit isolates. Likewise, very high prevalence of pfhA gene (95.3%) was observed among Indian isolates, irrespective of host species origin.