Mechanism Underlying Defective Interferon Gamma-Induced IDO Expression in Non-obese Diabetic Mouse Fibroblasts

Indoleamine 2,3-dioxygenase (IDO) can locally suppress T cell-mediated immune responses. It has been shown that defective self-tolerance in early prediabetic female non-obese diabetic (NOD) mice can be attributed to the impaired interferon-gamma (IFN-γ)- induced IDO expression in dendritic cells of these animals. As IFN-γ can induce IDO in both dendritic cells and fibroblasts, we asked the question of whether there exists a similar defect in IFN-γ-induced IDO expression in NOD mice dermal fibroblasts. To this end, we examined the effect of IFN-γ on expression of IDO and its enzymatic activity in NOD dermal fibroblasts. The results showed that fibroblasts from either prediabetic (8 wks of age) female or male, and diabetic female or male (12 and 24 wks of age respectively) NOD mice failed to express IDO in response to IFN-γ treatment. To find underlying mechanisms, we scrutinized the IFN- γ signaling pathway and investigated expression of other IFN-γ-modulated factors including major histocompatibility complex class I (MHC-I) and type I collagen (COL-I). The findings revealed a defect of signal transducer and activator of transcription 1 (STAT1) phosphorylation in NOD cells relative to that of controls. Furthermore, we found an increase in MHC-I and suppression of COL-I expression in fibroblasts from both NOD and control mice following IFN-γ treatment; indicating that the impaired response to IFN-γ in NOD fibroblasts is specific to IDO gene. Finally, we showed that an IFN-γ-independent IDO expression pathway i.e. lipopolysaccharide (LPS)-mediated-c-Jun kinase is operative in NOD mice fibroblast. In conclusion, the findings of this study for the first time indicate that IFN-γ fails to induce IDO expression in NOD dermal fibroblasts; this may partially be due to defective STAT1 phosphorylation in IFN-γ-induced-IDO signaling pathway

Implementation of computational methods to pattern recognition of movement behavior of Blattella germanica (Blattaria : Blattellidae) treated with Ca2+ signal inducing chemicals

Response behavior of specimens of the German cockroach (Blattella germanica) exposed to the Ca2+ signal inducing chemicals was characterized through implementation of two computational methods: the Fourier transform analysis and artificial neural networks. lonomycin, thapsigargin, and their solvent (dimethyl sulfoxide) were topically applied to male German cockroaches, and the movement tracks were continuously observed through the image processing system under semi-natural conditions for 4-5 days. The specimens treated with the chemicals revealed different movement patterns: 1) shaky advancement and entanglement of the movement tracks with the ionomycin treatments; 2) continuous, circular movements with the thapsigargin treatments; and 3) shaky turning movements with the dimethyl sulfoxide treatments. The movement tracks in time domain were further analyzed with the two-dimensional fast Fourier transform (2-D FFT). The coefficients of the 2-D FFT efficiently revealed characteristics that resided in the two-dimensional data of the movement tracks in the frequency domain. Subsequently the magnitudes of the coefficients were trained by self-organizing map (SOM) through unsupervised learning. Classification of the different movement patterns was possible with the trained network. The combined use of the 2-D FFT and the SOM could be an alternative tool to automatically monitor behavioral changes in specimens exposed to stimulating chemicals.X1125sciescopu

Impaired expression of indoleamine 2, 3-dioxygenase in monocyte-derived dendritic cells in response to Toll-like receptor-7/8 ligands

The effects of immunostimulatory RNAs (isRNAs) on the expression of immuno-suppressive factors are largely unknown. Indoleamine 2,3-dioxygenase (IDO) is a key negative regulator of immune responses and it has been implicated in hampering immunity against tumours. Here we show that the activation of Toll-like receptors (TLR)-7/8 with isRNAs or R848, a specific ligand for TLR7/8, can induce IDO expression in human monocytes, but not in monocyte-derived dendritic cells (moDC). In contrast to TLR7/8 agnosists, treatment of the same moDC with interferon-γ-induced IDO expression. Treatment of monocytes with 2′-O-methyl uridine-modified isRNAs alone does not induce IDO, but totally abrogated the effects of unmodified isRNAs. Like isRNAs, synthetic viral RNAs and cytomegalovirus (CMV) induced IDO in monocytes, whereas TLR2 ligand lipopeptide Pam3Cys exhibited no effect. Furthermore, IDO positive monocytes suppressed autologous T-cell activation. Collectively, these data indicate for first time that the potency of TLR7/8 signalling pathways to induce IDO expression in monocytes is silenced when the cells are programmed to differentiate into dendritic cells. The immunosuppressive properties of IDO might confer an advantage to CMV-infected monocytes to escape T-cell responses. The findings that 2′-O-methyl modified RNAs can block isRNA-induced IDO expression would facilitate the design of new TLR inhibitors

Allelopathic and autotoxicity effects of barley (Hordeum vulgare L. ssp. vulgare) root exudates

The allelopathic activity of barley (Hordeum vulgare L. ssp. vulgare) root exudates was studied by comparing their effects on seedling establishment in barley itself and in two weed species, Bromus diandrus Roth. and Lolium rigidum Gaudin, using an original laboratory protocol, named ‘seed-after-seed’. In this protocol, the donor and the receiver species of watersoluble allelochemicals are grown one after the other in the same dishes, in conditions reducing resource competition between both species. Growth of all receptive species (weeds and barley) was inhibited in a dose-dependent manner, when using increasing barley seed densities (0, 8, 19 and 25 seeds per Petri dish). In our conditions, the barley varieties and landraces exhibited different allelopathic activities against weeds or barley. The allelopathic potential of the barley root exudates was also dependent on the receiver species. Indeed, the released allelochemicals proved to be more toxic against the weed plants than on barley itself. Furthermore, the toxicity of the allelochemicals increased after their release by roots, between day 0 and day 6. These allelochemicals might contribute to the plant community dynamics and their usefulness as bio-herbicides deserves further consideration