Orphanin FQ/nociceptin interactions with the immune system in vivo: Gene expression changes in lymphoid organs and regulation of the cytokine response to staphylococcal enterotoxin A

2006 ◽  
Vol 176 (1-2) ◽  
pp. 76-85 ◽  
Author(s):  
Yael Goldfarb ◽  
Rainer K. Reinscheid ◽  
Alexander W. Kusnecov
Keyword(s):  
Gene Expression ◽  
Immune System ◽  
Staphylococcal Enterotoxin ◽  
Cytokine Response ◽  
Lymphoid Organs ◽  
Staphylococcal Enterotoxin A ◽  
Orphanin Fq

scholarly journals Effect of (−)-Epigallocatechin Gallate to Staphylococcal Enterotoxin A on Toxin Activity

Molecules ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 1867
Author(s):  
Yuko Shimamura ◽  
Mio Utsumi ◽  
Chikako Hirai ◽  
Ami Kurokawa ◽  
Toshiyuki Kan ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Epigallocatechin Gallate ◽  
Direct Interaction ◽  
Model Solution ◽  
Staphylococcal Enterotoxin ◽  
Hydroxyl Group ◽  
Staphylococcal Enterotoxin A ◽  
Toxic Activity ◽  
Alkaline Conditions

Staphylococcal enterotoxin A (SEA) functions both as superantigens that stimulate non-specific T cell proliferation as well as potent gastrointestinal toxins. We previously reported that (−)-epigallocatechin gallate (EGCG) binds to SEA. Therefore, the ability of EGCG to inhibit SEA toxin activity was examined. As a result, EGCG significantly decreased SEA-induced expression and production of interferon gamma (IFN-γ). In addition, EGCG inhibited SEA-induced spleen cell proliferation. To investigate the role of the galloyl group in EGCG on SEA cytotoxicity in more detail, the effect of the binding of a hydroxyl group at position 3 of the galloyl group in EGCG to SEA on SEA cytotoxicity was examined using two methylated EGCG. SEA cytotoxicity was significantly controlled in both (−)-3′′-Me-EGCG and (−)-4′′-Me-EGCG. These results suggest that EGCG inhibits toxic activity via direct interaction with SEA or without any interaction with SEA. The binding affinity between SEA and EGCG under in vivo conditions was examined using a model solution. Although after treatment under acidic and alkaline conditions, the presence of protein and the digestive tract model solution, EGCG still interacted with SEA. Our studies are the first to demonstrate the effect of the binding of EGCG to SEA on toxin activity.

scholarly journals Mouse Model for the Equilibration Interaction between the Host Immune System and Human T-Cell Leukemia Virus Type 1 Gene Expression

2002 ◽  
Vol 76 (6) ◽  
pp. 2703-2713 ◽  
Author(s):  
Rika A. Furuta ◽  
Kikuya Sugiura ◽  
Shigenari Kawakita ◽  
Takefumi Inada ◽  
Susumu Ikehara ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune System ◽  
Leukemia Virus ◽  
Host Immune System ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus

ABSTRACT To study the involvement of immune responses against Tax of human T-cell leukemia virus type 1 (HTLV-1) in the growth of and gene suppression in Tax-expressing tumor cells in vivo, we established a model system involving C57BL/6J mice and a syngeneic lymphoma cell line, EL4. When mice were immunized by DNA-based immunization with Tax expression plasmids, solid tumor formation upon subcutaneous inoculation of EL4 cells expressing green fluorescent protein-fused Tax (Gax) under the control of the HTLV-1 enhancer was strongly inhibited, and in vitro analysis showed that DNA immunization elicited cytotoxic T-lymphocyte (CTL) responses but not production of antibodies to Tax protein. Since EL4/Gax cells inoculated into DNA-immunized mice were not completely eradicated but were maintained as small solid tumors for a long period, there appeared to be a certain equilibrium between CTL activity and the growth of Gax-expressing cells. With such a balance, expression of the Gax gene in EL4/Gax cells was strongly suppressed. These results suggested that gene expression under the control of the HTLV-1 long terminal repeat and Tax is silenced in vivo, resulting in an equilibrium between viral expression and the host immune system. Such a balance would represent a status of persistent infection by HTLV-1 in virus-infected individuals during the latency period.

scholarly journals Early gene expression changes induced by the bacterial superantigen staphylococcal enterotoxin B and its modulation by a proteasome inhibitor

2009 ◽  
Vol 37 (3) ◽  
pp. 279-293 ◽  
Author(s):  
Govindarajan Rajagopalan ◽  
Ashenafi Y. Tilahun ◽  
Yan W. Asmann ◽  
Chella S. David
Keyword(s):  
Gene Expression ◽  
Proteasome Inhibitor ◽  
Dna Microarrays ◽  
Serum Levels ◽  
Staphylococcal Enterotoxin ◽  
Early Gene ◽  
Staphylococcal Enterotoxin B ◽  
Molecular Events ◽  
Enterotoxin B

Toxic shock syndrome (TSS) is an acute, serious systemic illness caused by bacterial superantigens. Nonavailability of a suitable animal model until recently has hampered an in-depth understanding of the pathogenesis of TSS. In the current study, we characterized the early molecular events underlying TSS using our HLA-DR3 transgenic mouse model. Gene expression profiling using DNA microarrays identified a rapid and significant upregulation of several pro- as well as anti-inflammatory mediators, many of which have never been previously described in TSS. In vivo administration of staphylococcal enterotoxin B (SEB) led to an increase in the expression of Th0- (IL-2, 240-fold); Th1- (IFN-γ, 360-fold; IL-12, 8-fold); Th2- (IL-4, 53-fold; IL-5, 4-fold) as well as Th17-type cytokines (IL-21, 19-fold; IL-17, 5-fold). The immunoregulatory cytokines (IL-6, 700-fold; IL-10, 18-fold); CC chemokines (such as CCL 2, 11, 3, 24, 17, 12, 7), CXC chemokines (such as CXCL 1, 2, 5, 11, 10, 19); and several proteases (matrix metalloproteinases 13, 8, 3, and 9) were also upregulated. Serum levels of several of these cytokines/chemokines were also significantly elevated. Pathway analyses revealed significant modulation in a variety of biochemical and cellular functions, providing molecular insights into the pathogenesis of TSS. Administration of bortezomib, a clinically approved proteasome inhibitor capable of blocking NF-κB pathway, was able to significantly modulate the expression of a variety of genes induced by SEB. Thus, our study showed that TSS is a complex process and emphasized the potential of use of bortezomib in the therapy of superantigen-induced TSS.

scholarly journals Lactobacillus reuteri-derived extracellular vesicles maintain intestinal immune homeostasis against lipopolysaccharide-induced inflammatory responses in broilers

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Rujiu Hu ◽  
Hua Lin ◽  
Mimi Wang ◽  
Yuezhen Zhao ◽  
Haojing Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune System ◽  
Extracellular Vesicles ◽  
Lactobacillus Reuteri ◽  
Inflammatory Responses ◽  
Immune Homeostasis ◽  
Tnf Α ◽  
Chicken Model

Abstract Background Lactobacillus reuteri strains are widely used as probiotics to prevent and treat inflammatory bowel disease by modulating the host’s immune system. However, the underlying mechanisms by which they communicate with the host have not been clearly understood. Bacterial extracellular vesicles (EVs) have been considered as important mediators of host-pathogen interactions, but their potential role in commensals-host crosstalk has not been widely studied. Here, we investigated the regulatory actions of EVs produced by L. reuteri BBC3, a gut-associated commensal bacterium of Black-Bone chicken, in the development of lipopolysaccharide (LPS)-induced intestinal inflammation in a chicken model using both in vivo and in vitro experiments. Results L. reuteri BBC3 produced nano-scale membrane vesicles with the size range of 60–250 nm. Biochemical and proteomic analyses showed that L. reuteri BBC3-derived EVs (LrEVs) carried DNA, RNA and several bioactive proteins previously described as mediators of other probiotics’ beneficial effects such as glucosyltransferase, serine protease and elongation factor Tu. In vivo broiler experiments showed that administration of LrEVs exerted similar effects as L. reuteri BBC3 in attenuating LPS-induced inflammation by improving growth performance, reducing mortality and decreasing intestinal injury. LrEVs suppressed the LPS-induced expression of pro-inflammatory genes (TNF-α, IL-1β, IL-6, IL-17 and IL-8), and improved the expression of anti-inflammatory genes (IL-10 and TGF-β) in the jejunum. LrEVs could be internalized by chicken macrophages. In vitro pretreatment with LrEVs reduced the gene expression of TNF-α, IL-1β and IL-6 by suppressing the NF-κB activity, and enhanced the gene expression of IL-10 and TGF-β in LPS-activated chicken macrophages. Additionally, LrEVs could inhibit Th1- and Th17-mediated inflammatory responses and enhance the immunoregulatory cells-mediated immunosuppression in splenic lymphocytes of LPS-challenged chickens through the activation of macrophages. Finally, we revealed that the reduced content of both vesicular proteins and nucleic acids attenuated the suppression of LrEVs on LPS-induced inflammatory responses in ex vivo experiments, suggesting that they are essential for the LrEVs-mediated immunoregulation. Conclusions We revealed that LrEVs participated in maintaining intestinal immune homeostasis against LPS-induced inflammatory responses in a chicken model. Our findings provide mechanistic insight into how commensal and probiotic Lactobacillus species modulate the host’s immune system in pathogens-induced inflammation.

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