Regulation of T Cell Function by Reactive Nitrogen and Oxygen Species in Collagen-Induced Arthritis.

Aims: In this study, we investigate the role of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in autoimmune diseases. We focus on oxidative regulation at the interaction between antigen-presenting cells (APCs) and T cells, and consequent effect of ROS and RNS on type II collagen (CII)-induced arthritis (CIA) model in mice. Results: Mice deficient in ROS and peroxide, due to a mutation in Ncf1 gene, develop an exaggerated CIA and a stronger T cell response to CII. In contrast, nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) was found to protect against CIA. The most pronounced protective effect was observed when L-NAME treatment started immediately after CII immunization. Ten days after immunization, the CII-reactive T cell-proliferative response was greater in Ncf1-mutant mice that were treated with L-NAME. T cells from L-NAME-treated mice, primed with CII, showed lower interleukin-2 secretion in response to CII in vitro. Moreover, inhibition of RNS production resulted in dysregulation of NOS1 (neuronal) expression in CII-reactive T cells. Innovation and Conclusion: The results support that deficiency of a paracrine factor as ROS and peroxide released by APC leads to pronounced activation of T cells and enhanced arthritis. An intrinsic factor might be RNS produced by NOS1, which likely enhanced T cell activation in an autocrine manner.

Limiting immunopathology: Interaction between carotenoids and enzymatic antioxidant defences.

The release of reactive oxygen and nitrogen species (ROS and RNS) during the inflammatory response generates damages to host tissues, referred to as immunopathology, and is an important factor in ecological immunology. The integrated antioxidant system, comprising endogenous antioxidant enzymes (e.g. superoxide dismutase SOD, and catalase CAT) and dietary antioxidants (e.g. carotenoids), helps to cope with immune-mediated oxidative stress. Crustaceans store large amounts of dietary carotenoids for yet unclear reasons. While being immunostimulants and antioxidants, the interaction of these pigments with antioxidant enzymes remains unclear. Here, we tested the interaction between dietary supplementation with carotenoids and immune challenge on immune defences and the activity of the antioxidant enzymes SOD and CAT, in the amphipod crustacean Gammarus pulex. Dietary supplementation increased the concentrations of circulating carotenoids and haemocytes in the haemolymph, while the immune response induced the consumption of circulating carotenoids and a drop of haemocyte density. Interestingly, supplemented gammarids exhibited down-regulated SOD activity but high CAT activity compared to control ones. Our study reveals specific interactions of dietary carotenoids with endogenous antioxidant enzymes, and further underlines the potential importance of carotenoids in the evolution of immunity and/or of antioxidant mechanisms in crustaceans.

[The effect of Xinfeng capsule treatment on the number of BTLA(+)T cells and oxidative stress of patients with ankylosing spondylitis].

OBJECTIVE: To investigate the changes of B and T lymphocyte attenuator (BTLA), reactive oxygen species (ROS), reactive nitrogen species (RNS), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), total antioxidative capacity (TAOC) in the patients with ankylosing spondylitis (AS) and the effect of Xinfeng capsule (XFC) on them. METHODS: AS patients (n=140) were randomly divided into two groups, XFC group (3 tablets each time, tid, n=70) and salicylazosulfapyridine (SASP) group (4 pills each time, bid, n=70). Continuous treatment lasts 3 months. The study also enrolled 60 healthy volunteers as a control group. Flow cytometry was used to test BTLA expression. ELISA was performed to detect the oxidative stress indicators (ROS, RNS, MDA, SOD, CAT, TAOC) and cytokines (IL-4, IL-10, IL-1ß, TNF-α). Western blotting was adopted to examine the blood sedimentation (ESR). HITACHI 7060 automatic biochemical analyzer was used to determine the level of high sensitive C-reactive protein (Hs-CRP). RESULTS: Clinical efficacy of XFC group was significantly better than that of SASP group (P<0.01). Compared with the healthy control group, AS patients had significantly lower BTLA expression in CD3(+) T cells and CD4(+) T cells from the peripheral blood (P<0.01 or P<0.05), the decreased levels of SOD, CAT and TAOC, and significantly increased ROS, RNS and MDA values (P<0.01 or P<0.05). In addition, the levels of serum IL-1ß, TNF-α, ESR and Hs-CRP were significantly higher (P<0.01) and IL-4, IL-10 were significantly lower in AS patients (P<0.01 or P<0.05). Compared with pre-treatment, both XFC and SASP significantly elevated the expressions of BTLA(+)CD3(+) T, BTLA(+)CD4(+) T, BTLA, SOD, TAOC, IL-4, SF-36 (PF, SF, RP, RE, BP, MH, VT, GH) eight dimension scores, and reduced ROS, MDA, TNF-α, ESR, Hs-CRP, VAS, BASDAI, BASFI and BAS-G in the peripheral blood (P<0.01 or P<0.05). The differences between XFC group and SASP group were statistically significant (P<0.01 or P<0.05). Pearson correlation analysis showed that BTLA expression level in the peripheral blood was positively correlated with SOD, RP, BP, SF and RE. BTLA(+)CD3(+) T cells and BTLA*CD4(+) T cells were significantly negatively correlated with ROS, MDA, IL-1ß, TNF-α, ESR, VAS and BASDAI, and they were positively correlated with TAOC, IL-4 and IL-10. BTLA(+)CD3(+) T cells were significantly negatively correlated with RNS, Hs-CRP and BASFI; BTLA(+)CD4(+) T cells were positively correlated with CAT. CONCLUSION: XFC can improve BTLA expression in the peripheral blood of AS patients and regulate negatively the activation and proliferation of T cells.

Non-specific immune response and disease resistance induced by Siegesbeckia glabrescens against Vibrio parahaemolyticus in Epinephelus bruneus.

The immunomodulatory effect of Siegesbeckia glabrescens extract-supplementation diets on innate immune response and disease resistance of kelp grouper, Epinephelus bruneus against Vibrio parahaemolyticus at weeks 1, 2, and 4 is reported. The serum lysozyme activity was significantly enhanced with any enriched diet from weeks 1-4 when compared to control diet (0%). The alternative complement haemolytic activities significantly were enhanced with all enriched diets on weeks 2 and 4 whereas the cellular reactive oxygen species (ROS) was significantly enhanced only with 1.0% and 2.0% diets. The reactive nitrogen intermediate (RNI) value was significantly enhanced with any enriched diet on weeks 2 and 4, but on first week it did not differ from control. The myeloperoxidase (MPO) production significantly increased with 1.0% and 2.0% diets from second week onwards; with other enriched diets the increase manifested on fourth week; but during first week it did not vary from that of the control with any enriched diet. The protection in terms of cumulative mortality was the least being 25% and 20% when fed with 1.0% and 2.0% diets. The present results indicate that feeding kelp grouper with S. glabrescens extract enriched diet at 1.0% and 2.0% levels significantly enhance the immunological parameters, increase the disease resistance and minimize the cumulative mortality in E. bruneus against V. parahaemolyticus.

Effect of Coriolus versicolor supplemented diet on innate immune response and disease resistance in kelp grouper Epinephelus bruneus against Listonella anguillarum.

The effect of Coriolus versicolor extract supplemented diets on innate immune response and disease resistance in kelp grouper, Epinephelus bruneus against Listonella anguillarum, is reported. Kelp grouper were divided into four groups of 25 each and fed with C. versicolor enriched diets at 0% (control), 0.01%, 0.1%, and 1.0% level. After 30 days of feeding, all fish were injected interaperitoneally (i.p.) with 50 µl of L. anguillarum (4.7 × 10(7) CFU) to investigate the immune parameters at weeks 1, 2, and 4. The reactive oxygen species and reactive nitrogen species production were significantly enhanced in fish fed with 0.1% and 1.0% supplementation diets from weeks 1-4 when compared to the non enriched diet fed and infected control. The phagocytic activity significantly increased with 0.1% and 1.0% diets on weeks 2 and 4. The leucocyte myeloperoxidase content, lysozyme activity, and total protein level significantly increased when fed with 0.1% and 1.0% supplementation diets from weeks 1-4. The cumulative mortality was 35% and 45% in 1.0% and 0.1% enriched diet fed groups whereas it was 55% and 80% in 0.01% and 0% groups respectively. The present results suggest that diets enriched with C. versicolor at 0.1% or 1.0% level positively enhance the innate immune system and affords protection from L. anguillarum.

Enhancement of nonspecific immunity and disease resistance in Oreochromis mossambicus by Solanum trilobatum leaf fractions.

The purpose of this study was to determine the effect of water and hexane soluble fractions of the Indian medicinal plant, Solanum trilobatum on the nonspecific immune mechanisms and disease resistance in Oreochromis mossambicus. Fish were intraperitoneally injected with different doses of 0, 4, 40 or 400 mg kg(-1) body weight of water or hexane soluble fraction. The nonspecific immune mechanisms were assessed in terms of serum lysozyme activity, reactive oxygen species production and reactive nitrogen species production by peripheral blood leucocytes. The functional immunity in terms of percentage mortality and Relative Percent Survival (RPS) was assessed by a challenge with live Aeromonas hydrophila. Almost all the doses of both water and hexane soluble fractions enhanced the serum lysozyme activity. All the doses of water soluble fraction significantly enhanced the ROS production on most of the days tested. In hexane soluble fraction treated groups, the enhancement in the ROS production was observed at least on 2 days. All the doses of water soluble fraction significantly enhanced the production of RNS only on one day. The RNS production was enhanced significantly only in the group treated with 40 mg kg(-1) of hexane fraction. The leaf fraction administration preceding the challenge with live A. hydrophila, decreased the percentage mortality in the experimental group with the consequent increase in RPS values. This preliminary study indicates that S. trilobatum could be used to promote the health status of fish in intensive finfish aquaculture.