The ligands of translocator protein inhibit human Th1 responses and the rejection of murine skin allografts

2017 ◽  
Vol 131 (4) ◽  
pp. 297-308 ◽  
Author(s):  
Yannan Zhang ◽  
Sifei Yu ◽  
Xiaomin Li ◽  
Binyan Yang ◽  
Changyou Wu
Keyword(s):  
Signal Transduction ◽  
Immune Responses ◽  
Inflammatory Cytokines ◽  
Translocator Protein ◽  
Th1 Cells ◽  
Skin Allografts ◽  
Tcr Signal Transduction

TSPO ligands inhibited the immune responses of human Th1 cells through interfering with TCR signal transduction and prevented the rejection of murine skin allografts by inhibiting the infiltration of cells and production of inflammatory cytokines.

scholarly journals Modulation of Bovine Endometrial Cell Receptors and Signaling Pathways as a Nanotherapeutic Exploration against Dairy Cow Postpartum Endometritis

Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1516
Author(s):  
Ayodele Olaolu Oladejo ◽  
Yajuan Li ◽  
Xiaohu Wu ◽  
Bereket Habte Imam ◽  
Jie Yang ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Signaling Pathways ◽  
Inflammatory Cytokines ◽  
Signal Transduction Pathway ◽  
Endometrial Cell ◽  
Cell Receptors ◽  
Endometrial Cells ◽  
Microbial Invasion ◽  
Pass Through ◽  
Pro Inflammatory Cytokines

In order to control and prevent bovine endometritis, there is a need to understand the molecular pathogenesis of the infectious disease. Bovine endometrium is usually invaded by a massive mobilization of microorganisms, especially bacteria, during postpartum dairy cows. Several reports have implicated the Gram-negative bacteria in the pathogenesis of bovine endometritis, with information dearth on the potentials of Gram-positive bacteria and their endotoxins. The invasive bacteria and their ligands pass through cellular receptors such as TLRs, NLRs, and biomolecular proteins of cells activate the specific receptors, which spontaneously stimulates cellular signaling pathways like MAPK, NF-kB and sequentially triggers upregulation of pro-inflammatory cytokines. The cascade of inflammatory induction involves a dual signaling pathway; the transcription factor NF-κB is released from its inhibitory molecule and can bind to various inflammatory genes promoter. The MAPK pathways are concomitantly activated, leading to specific phosphorylation of the NF-κB. The provision of detailed information on the molecular pathomechanism of bovine endometritis with the interaction between host endometrial cells and invasive bacteria in this review would widen the gap of exploring the potential of receptors and signal transduction pathways in nanotechnology-based drug delivery system. The nanotherapeutic discovery of endometrial cell receptors, signal transduction pathway, and cell biomolecules inhibitors could be developed for strategic inhibition of infectious signals at the various cell receptors and signal transduction levels, interfering on transcription factors activation and pro-inflammatory cytokines and genes expression, which may significantly protect endometrium against postpartum microbial invasion.

scholarly journals Characterization of the Kaposi's Sarcoma-Associated Herpesvirus K1 Signalosome

2005 ◽  
Vol 79 (19) ◽  
pp. 12173-12184 ◽  
Author(s):  
Bok-Soo Lee ◽  
Sun-Hwa Lee ◽  
Pinghui Feng ◽  
Heesoon Chang ◽  
Nam-Hyuk Cho ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Inflammatory Cytokines ◽  
Kaposi's Sarcoma ◽  
Mutational Analysis ◽  
Tyrosine Phosphatase ◽  
Kaposi’S Sarcoma ◽  
Sh2 Domain ◽  
Signaling Proteins ◽  
Cellular Signal ◽  
Cellular Components

ABSTRACT Kaposi's sarcoma (KS) is a multifocal angiogenic tumor and appears to be a hyperplastic disorder caused, in part, by local production of inflammatory cytokines. The K1 lymphocyte receptor-like protein of KS-associated herpesvirus (KSHV) efficiently transduces extracellular signals to elicit cellular activation events through its cytoplasmic immunoreceptor tyrosine-based activation motif (ITAM). To further delineate K1-mediated signal transduction, we purified K1 signaling complexes and identified its cellular components. Upon stimulation, the K1 ITAM was efficiently tyrosine phosphorylated and subsequently interacted with cellular Src homology 2 (SH2)-containing signaling proteins Lyn, Syk, p85, PLCγ2, RasGAP, Vav, SH2 domain-containing protein tyrosine phosphatase 1/2, and Grab2 through its phosphorylated tyrosine residues. Mutational analysis demonstrated that each tyrosine residue of K1 ITAM contributed to the interactions with cellular signaling proteins in distinctive ways. Consequently, these interactions led to the marked augmentation of cellular signal transduction activity, evidenced by the increase of cellular tyrosine phosphorylation and intracellular calcium mobilization, the activation of NF-AT and AP-1 transcription factor activities, and the production of inflammatory cytokines. These results demonstrate that KSHV K1 effectively recruits a set of cellular SH2-containing signaling molecules to form the K1 signalosome, which elicits downstream signal transduction and induces inflammatory cytokine production.

scholarly journals Host F-box protein 22 enhances the uptake of Brucella by macrophages and drives a sustained release of pro-inflammatory cytokines through degradation of the anti-inflammatory effector proteins of Brucella.

2021 ◽  
Author(s):  
Girish Radhakrishnan ◽  
Varadendra Mazumdar ◽  
Kiranmai Joshi ◽  
Binita Roy Nandi ◽  
Swapna Namani ◽  
...  
Keyword(s):  
Immune Responses ◽  
Inflammatory Cytokines ◽  
Effector Proteins ◽  
Host Protein ◽  
Limited Information ◽  
Phagocytic Cells ◽  
Scf Complex ◽  
Enhanced Production ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Brucella species are intracellular bacterial pathogens, causing the world-wide zoonotic disease, brucellosis.  Brucella invade professional and non-professional phagocytic cells, followed by resisting intracellular killing and establishing a replication permissive niche. Brucella also modulate the innate and adaptive immune responses of the host for their chronic persistence. The complex intracellular cycle of Brucella majorly depends on multiple host factors but limited information is available on host and bacterial proteins that play essential role in the invasion, intracellular replication and modulation of host immune responses. By employing an siRNA screening, we identified a role for the host protein, FBXO22 in Brucella -macrophage interaction. FBXO22 is the key element in the SCF E3 ubiquitination complex where it determines the substrate specificity for ubiquitination and degradation of various host proteins.  Downregulation of FBXO22 by siRNA or CRISPR-Cas9 system, resulted diminished uptake of Brucella into macrophages, which was dependent on NF-κB-mediated regulation of phagocytic receptors. FBXO22 expression was upregulated in Brucella -infected macrophages that resulted induction of phagocytic receptors and enhanced production of pro-inflammatory cytokines through NF-κB. Furthermore, we found that FBXO22 recruits the effector proteins of Brucella , including the anti-inflammatory proteins, TcpB and OMP25 for degradation through the SCF complex. We did not observe any role for another F-box containing protein of SCF complex, β-TrCP in Brucella -macrophage interaction. Our findings unravel novel functions of FBXO22 in host-pathogen interaction and its contribution to pathogenesis of infectious diseases.

scholarly journals The Murine CD137/CD137 Ligand Signalosome: A Signal Platform Generating Signal Complexity

2020 ◽  
Vol 11 ◽  
Author(s):  
Beom K. Choi ◽  
Hyeon-Woo Lee
Keyword(s):  
Signal Transduction ◽  
Immune Responses ◽  
Immune Cells ◽  
Expression Patterns ◽  
Costimulatory Receptor ◽  
Spatiotemporal Expression ◽  
Paradoxical Effects ◽  
Signal Complexity ◽  
Proximal Signaling ◽  
Deficient Mice

CD137, a member of the TNFR family, is a costimulatory receptor, and CD137L, a member of the TNF family, is its ligand. Studies using CD137- and CD137L-deficient mice and antibodies against CD137 and CD137L have revealed the diverse and paradoxical effects of these two proteins in various cancers, autoimmunity, infections, and inflammation. Both their cellular diversity and their spatiotemporal expression patterns indicate that they mediate complex immune responses. This intricacy is further enhanced by the bidirectional signal transduction events that occur when these two proteins interact in various types of immune cells. Here, we review the biology of murine CD137/CD137L, particularly, the complexity of their proximal signaling pathways, and speculate on their roles in immune responses.

scholarly journals Regulation of Antitumor Immune Responses by the IL-12 Family Cytokines, IL-12, IL-23, and IL-27

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Mingli Xu ◽  
Izuru Mizoguchi ◽  
Noriko Morishima ◽  
Yukino Chiba ◽  
Junichiro Mizuguchi ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Th17 Cells ◽  
Antitumor Immunity ◽  
Inflammatory Responses ◽  
Memory T Cells ◽  
Th1 Cells ◽  
Signal Transducers ◽  
Th Cell ◽  
Antigen Presenting

The interleukin (IL)-12 family, which is composed of heterodimeric cytokines including IL-12, IL-23, and IL-27, is produced by antigen-presenting cells such as macrophages and dendritic cells and plays critical roles in the regulation of helper T (Th) cell differentiation. IL-12 induces IFN- production by NK and T cells and differentiation to Th1 cells. IL-23 induces IL-17 production by memory T cells and expands and maintains inflammatory Th17 cells. IL-27 induces the early Th1 differentiation and generation of IL-10-producing regulatory T cells. In addition, these cytokines induce distinct immune responses to tumors. IL-12 activates signal transducers and activator of transcription (STAT)4 and enhances antitumor cellular immunity through interferon (IFN)- production. IL-27 activates STAT1, as does IFN- and STAT3 as well, and enhances antitumor immunity by augmenting cellular and humoral immunities. In contrast, although exogenously overexpressed IL-23 enhances antitumor immunity via memory T cells, endogenous IL-23 promotes protumor immunity through STAT3 activation by inducing inflammatory responses including IL-17 production.

Plasmid DNA encoding influenza virus haemagglutinin induces Th1 cells and protection against respiratory infection despite its limited ability to generate antibody responses

Microbiology ◽  
2000 ◽  
Vol 81 (7) ◽  
pp. 1737-1745 ◽  
Author(s):  
Patricia A. Johnson ◽  
Margaret A. Conway ◽  
Janet Daly ◽  
Carolyn Nicolson ◽  
James Robertson ◽  
...  
Keyword(s):  
Influenza Virus ◽  
T Cell ◽  
Immune Responses ◽  
Plasmid Dna ◽  
Dna Vaccines ◽  
Dose Range ◽  
Th1 Cells ◽  
Dna Encoding ◽  
Live Virus ◽  
Limited Ability

Direct intramuscular injection of plasmid DNA can generate immune responses against encoded antigens. However, the relative ability of DNA vaccines to induce cellular and humoral immunity after a single or booster immunization and the persistence of this response have not been fully elucidated. In this study, induction and maintenance of antibody and T cell subtypes with different doses of naked DNA encoding the haemagglutinin (HA) gene of influenza virus were examined and compared to the immune responses and protection induced by respiratory tract infection and immunization with a killed virus vaccine. Like natural infection, immunization with HA DNA induced potent Th1 responses. Spleen cells from mice immunized once with HA DNA in the dose range 10 ng to 100 μg secreted significant levels of IFN-γ, but low or undetectable IL-5, in response to influenza virus in vitro. Furthermore, CD4+ HA-specific Th1 clones were generated from spleens of immunized mice. Although T cell responses waned 12 weeks after a single immunization, antigen-specific Th1 cells persisted in the spleen for at least 6 months after two booster immunizations. In contrast, influenza virus-specific ELISA IgG titres were low after a single immunization and required two booster immunizations to reach significant levels. Furthermore, haemagglutination inhibition (HI) antibodies were weak or undetectable after two immunizations. Nevertheless, two doses of HA DNA conferred almost complete protection against respiratory challenge with live virus. Thus, despite the limited ability to induce antibodies, DNA vaccines confer protective immunity against influenza virus infection, which appears to be mediated by Th1 cells.

Immune responses after influenza vaccination in patients of primary Sjögren’s syndrome

Rheumatology ◽  
2020 ◽  
Vol 60 (1) ◽  
pp. 224-230
Author(s):  
Xingyu Zhou ◽  
Yisi Liu ◽  
Yuebo Jin ◽  
Yifan Wang ◽  
Miao Miao ◽  
...  
Keyword(s):  
Immune Responses ◽  
Influenza Vaccination ◽  
Th17 Cells ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Primary Sjögren’S Syndrome ◽  
Th1 Cells ◽  
Primary Sjogren’S Syndrome ◽  
Primary Sjögren's Syndrome ◽  
Sjögren‘S Syndrome

Abstract Objectives Influenza vaccination is effective in preventing infections in most people. This study aimed to assess the changes of immune responses in primary Sjögren’s Syndrome (pSS) patients after influenza vaccination and determine the safety of influenza vaccination. Methods A total of 17 patients with pSS and 16 healthy controls (HCs) were included. Peripheral mononuclear cells were analysed by flow cytometry. Vaccine-specific antibodies were determined by ELISA. Clinical features and serological responses were monitored. Results The percentages of T follicular helper cell (Tfh) were significantly elevated in HCs after vaccination (P=0.0005), while no significant differences in the levels of Tfh in pSS patients were identified (P=0.1748). The proportions of Th2 cells were significantly decreased after vaccination in both pSS patients and HCs (P<0.05). In contrast, the percentages of Th1 cells and Th17 cells were significantly increased after vaccination in pSS patients (P<0.05), while no significant differences in the percentages of Th1 and Th17 cells were identified in HCs (P>0.05), although a trend towards higher levels of Th1 cells was observed (P=0.0830). No significant changes in the proportions of memory B cells and plasmablasts were observed after vaccination. Patients with pSS developed higher levels of vaccine-specific IgGs compared with HCs (P=0.001). No significant changes in disease manifestations and laboratory parameters were observed after vaccination. No increased vaccination related adverse effect was observed in pSS. Conclusion Our findings suggest the feasibility of applying influenza vaccines to patients with pSS, raising awareness for vaccination among the rheumatology community and involved healthcare professionals.

scholarly journals Polyamine Transport Protein PotD Protects Mice against Haemophilus parasuis and Elevates the Secretion of Pro-Inflammatory Cytokines of Macrophage via JNK–MAPK and NF–κB Signal Pathways through TLR4

Vaccines ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 216 ◽  
Author(s):  
Ke Dai ◽  
Xiaoyu Ma ◽  
Zhen Yang ◽  
Yung-Fu Chang ◽  
Sanjie Cao ◽  
...  
Keyword(s):  
Immune Responses ◽  
Inflammatory Cytokines ◽  
Transport System ◽  
Signal Pathways ◽  
Raw 264.7 ◽  
Raw 264.7 Macrophages ◽  
Cellular Immune Responses ◽  
Polyamine Transport ◽  
Cellular Immune ◽  
Pro Inflammatory Cytokines

The potD gene, belonging to the well-conserved ABC (ATP-binding cassette) transport system potABCD, encodes the bacterial substrate-binding subunit of the polyamine transport system. In this study, we found PotD in Haemophilus (Glaesserella) parasuis could actively stimulate both humoral immune and cellular immune responses and elevate lymphocyte proliferation, thus eliciting a Th1-type immune response in a murine immunity and infection model. Stimulation of Raw 264.7 macrophages with PotD validated that Toll-like receptor 4, rather than 2, participated in the positive transcription and expression of pro-inflammatory cytokines IL–1β, IL–6, and TNF–α using qPCR and ELISA. Blocking signal-regulated JNK–MAPK and RelA(p65) pathways significantly decreased PotD-induced pro-inflammatory cytokine production. Overall, we conclude that vaccination of PotD could induce both humoral and cellular immune responses and provide immunoprotection against H. parasuis challenge. The data also suggest that Glaesserella PotD is a novel pro-inflammatory mediator and induces TLR4-dependent pro-inflammatory activity in Raw 264.7 macrophages through JNK–MAPK and RelA(p65) pathways.

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