Interleukin-10 inhibits cytokine-mediated synergistic release of interleukin-6 in astrocytoma cells

Astrocytes respond to pro-inflammatory cytokines such as, interleukin-1 (IL-1beta) and tumor necrosis factor (TNF-alpha). However, the mechanisms in which IL-1beta and TNF-alpha mediate cell\u27s signaling need further investigation; In previous research, the effects of y-aminobutyric acid (GABA) on IL-1 and TNF-alpha signaling pathway were studied. GABA was unable to suppress IkappaB-alpha degradation and the phosphorylation of p38 by IL-1beta and TNF-alpha. However, it was suggested that GABA may be able to inhibit IL-6 release by reducing the rate of IkappaB-alpha degradation; Another cytokine, IL-10, which is well known in literature to have anti-inflammatory effects, is investigated in this study. This study presents IL-10 effects on the NF-kappaB and p38 signaling pathways as well as IL-10 inhibition of IL-1 and TNF synergistic induction of IL-6 release. The effect of other signaling molecules, believed to act as antagonists for p38 activation, were also investigated and presented in this study. Previous studies indicate that both IL-1beta and TNF-alpha were able to stimulate the phosphorylation of p38 and the degradation of NF-kappaB inhibitor, IkappaB-alpha, with no change in IkappaB-beta. While IL-10 is unable to suppress the phosphorylation of p38 by IL-1beta or TNF-alpha or degradation of IkappaB-alpha, inhibitor of NF-kappaB, it is also suggested that IL-10 may inhibit cytokine-mediated synergistic induction of IL-6 in mechanistically similar way to GABA; Inflammatory cytokines IL-1beta and TNF-alpha have repeatedly shown to phosphorylate p38 and activate NF-kappaB pathway. We also have shown their synergistic effect on release of extracellular IL-6 as well as synergistic increase in transcriptional activation of IL-6 mRNA. Anti-inflammatory effects of IL-10, GABA and p38 inhibitor SB203580 were also investigated. Experimental results suggest that neither IL-10 nor GABA can reverse p38 or NF-kappaB activation induced by IL-1beta and TNF-alpha. However, they inhibit synergistic release of IL-6 but have no effect on IL-6 transcriptional activation. Further, SB203580, inhibitor of p38, decreased synergistic mRNA transcript after stimulation with IL-1beta and TNF-alpha. Our findings may postulate that anti-inflammatory molecules such as GABA and IL-10 may have similar mode of action supposedly affecting post-translational mechanisms

Effect of the Predecessor and the Nitrogen Rate on Productivity and Essential Oil Content of Coriander (Coriandrum sativum L.) in Southeast Bulgaria

Received: May 31st, 2022 ; Accepted: August 13th, 2022 ; Published: September 19th, 2022 ; Correspondence: [email protected] (Coriandrum sativum L.) is one of the most important essential oil crops on a global scale. Coriander productivity is determined by the genotype, the environmental factors, as well the agronomic practices. A field experiment was conducted in Southeast Bulgaria during three vegetation seasons (2015, 2016, and 2017). The present study aimed at analysing the influence of two crop predecessors (winter wheat and sunflower) and four nitrogen (N) levels (0, 40, 80, and 120 kg ha-1 ). Productivity elements, seed yield, and seed essential oil content of coriander (cv. Mesten drebnoploden) were under evaluation. The results obtained showed that winter wheat was a more suitable predecessor of coriander in comparison to sunflower. The highest results regarding the number of umbels per plant, the umbel’s diameter, the number of umbellets per umbel, the number of seeds per umbel, the seed weight per plant, the 1,000 seed mass, as well as the seed yield for the rate of 80 kg ha-1 of N were recorded. The highest essential oil content after applying 120 kg ha-1 of N was established. Increasing the N level from 0 to 120 kg ha-1 led to a positive and significant effect on essential oil yield. No significant differences between the N rates of 80 and 120 kg ha-1 were recorded. The received results contributed for the evaluatation of the optimum nitrogen level, as well as for the determination of a more suitable predecessor of coriander in order to obtain the highest yield of better quality in the region of Southeast Bulgaria

The Antioxidant Role of Xanthurenic Acid in the Aedes aegypti Midgut during Digestion of a Blood Meal

In the midgut of the mosquito Aedes aegypti, a vector of dengue and yellow fever, an intense release of heme and iron takes place during the digestion of a blood meal. Here, we demonstrated via chromatography, light absorption and mass spectrometry that xanthurenic acid (XA), a product of the oxidative metabolism of tryptophan, is produced in the digestive apparatus after the ingestion of a blood meal and reaches milimolar levels after 24 h, the period of maximal digestive activity. XA formation does not occur in the White Eye (WE) strain, which lacks kynurenine hydroxylase and accumulates kynurenic acid. The formation of XA can be diminished by feeding the insect with 3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl] benzenesulfonamide (Ro-61-8048), an inhibitor of XA biosynthesis. Moreover, XA inhibits the phospholipid oxidation induced by heme or iron. A major fraction of this antioxidant activity is due to the capacity of XA to bind both heme and iron, which occurs at a slightly alkaline pH (7.5-8.0), a condition found in the insect midgut. The midgut epithelial cells of the WE mosquito has a marked increase in occurrence of cell death, which is reversed to levels similar to the wild type mosquitoes by feeding the insects with blood supplemented with XA, confirming the protective role of this molecule. Collectively, these results suggest a new role for XA as a heme and iron chelator that provides protection as an antioxidant and may help these animals adapt to a blood feeding habit

Laboratory and field experimental evaluation of host plant specificity of Aceria solstitialis, a prospective biological control agent of yellow starthistle

Centaurea solstitialis (yellow starthistle, Asteraceae) is an invasive annual weed in the western USA that is native to the Mediterranean Region and is a target for classical biological control. Aceria solstitialis is an eriophyid mite that has been found exclusively in association with Ce. solstitialis in Italy, Greece, Turkey and Bulgaria. The mite feeds on leaf tissue and damages bolting plants, causing stunting, witch’s broom and incomplete flower development. Field experiments and laboratory no-choice and two-way choice experiments were conducted to assess host plant specificity of the mite in Bulgaria. Mites showed the highest degree of host specificity in the field and lowest in the no-choice experiments. In the field, highest densities of mites occurred on Ce. solstitialis and Ce. cyanus (bachelor’s button), and either no mites or trace numbers occurred on the other test plants: Ce. diffusa (diffuse knapweed), Carthamus tinctorius (safflower) and Cynara scolymus (artichoke). In no-choice experiments, mites persisted for 60 days on Ce. diffusa, Ce. cyanus, Ce. solstitialis, Ca. tinctorius and Cy. scolymus, whereas in two-way choice experiments mites persisted on 25% of Cy. scolymus plants for 60 days and did not persist on Ca. tinctorius beyond 40 days. The eight other species of plants that were tested in the laboratory were less suitable for the mite. These results suggest that although A. solstitialis can persist on some nontarget plants for as long as 60 days in the laboratory, it appears to be much more specific under natural conditions, and warrants further evaluation as a prospective biological control agent