scholarly journals Absence of GdX/UBL4A protects against inflammatory bowel diseases by regulating NF-κB signaling in DCs and macrophages

2018 ◽  
Author(s):  
Chunxiao Liu ◽  
Yifan Zhou ◽  
Mengdi Li ◽  
Ying Wang ◽  
Shigao Yang ◽  
...  
Keyword(s):  
Immune Response ◽  
Inflammatory Diseases ◽  
Adaptor Protein ◽  
Endotoxin Shock ◽  
Innate Immune ◽  
Mucosal Inflammation ◽  
Innate Immune Responses ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Deficient Mice

AbstractNuclear factor-kappa B (NF-κB) activation is critical for innate immune responses. Here we report that the UBL4A (Ubiquitin-like protein 4A, also named GdX) enhances dendritic cells (DCs) and macrophages (Mφ)-mediated innate immune defenses by positively regulating NF-κB signaling. GdX-deficient mice were resistant to LPS-induced endotoxin shock and DSS-induced colitis. DC- or Mφ-specific GdX-deficient mice displayed alleviated mucosal inflammation, and the production of pro-inflammatory cytokines by GdX-deficient DCs and Mφ was reduced. Mechanistically, we found that PTPN2 (TC45) and PP2A form a complex with RelA (p65) to mediate its dephosphorylation whereas GdX interrupts the TC45/PP2A/p65 complex formation and restrict p65 dephosphorylation by trapping TC45. Our study provides a mechanism by which NF-κB signaling is positively regulated by an adaptor protein GdX in DC or Mφ to maintain the innate immune response. Targeting GdX could be a strategy to reduce over-activated immune response in inflammatory diseases.

scholarly journals Loss of Nckx3 Exacerbates Experimental DSS-Induced Colitis in Mice through p53/NF-κB Pathway

2021 ◽  
Vol 22 (5) ◽  
pp. 2645
Author(s):  
Dinh Nam Tran ◽  
Seon Myeong Go ◽  
Seon-Mi Park ◽  
Eui-Man Jung ◽  
Eui-Bae Jeung
Keyword(s):  
Immune Response ◽  
Cellular Proliferation ◽  
Intestinal Inflammation ◽  
Critical Role ◽  
Experimental Colitis ◽  
Innate Immune ◽  
Inflammatory Conditions ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Microarray Analyses

Inflammatory bowel diseases (IBDs) comprises a range of chronic inflammatory conditions of the intestinal tract. The incidence and prevalence of IBDs are increasing worldwide, but the precise etiology of these diseases is not completely understood. Calcium signaling plays a regulatory role in cellular proliferation. Nckx3, a potassium-dependent Na+/Ca2+ exchanger, is not only expressed in the brain but also in the aortic, uterine, and intestinal tissues, which contain abundant smooth muscle cells. This study investigated the role of Nckx3 in intestinal inflammation. Microarray analyses revealed the upregulation of the innate immune response-associated genes in the duodenum of Nckx3 knockout (KO) mice. The Nckx3 KO mice also showed an increase in IBD- and tumorigenesis-related genes. Using dextran sodium sulfate (DSS)-induced experimental colitis mice models, the Nckx3 KO mice showed severe colitis. Furthermore, the pathways involving p53 and NF-κB signaling were significantly upregulated by the absence of Nckx3. Overall, Nckx3 plays a critical role in the innate immune and immune response and may be central to the pathogenesis of IBD.

scholarly journals Blockade of PLD2 Ameliorates Intestinal Mucosal Inflammation of Inflammatory Bowel Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Guangxi Zhou ◽  
Lin Yu ◽  
Wenjing Yang ◽  
Wei Wu ◽  
Leilei Fang ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Blood Cells ◽  
Inflammatory Diseases ◽  
Critical Role ◽  
Neutrophil Migration ◽  
Mucosal Inflammation ◽  
Peripheral Blood Cells ◽  
Before And After ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Background. Inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are chronically remittent and progressive inflammatory disorders. Phospholipase D2 (PLD2) is reported to be involved in the pathogenesis of several inflammatory diseases. However, the exact role of PLD2 in IBD is obscure.Methods. PLD2 expression was determined in peripheral blood cells and inflamed mucosa from patients with IBD by qRT-PCR. Colonic biopsies were also obtained from CD patients before and after infliximab (IFX) treatment to examine PLD2 expression. PLD2 selective inhibitor (CAY10594) was administrated daily by oral gavage in DSS-induced colitis mice. Bone marrow neutrophils from colitis mice were harvested to examine the migration using Transwell plate.Results. PLD2 was found to be significantly increased in peripheral blood cells and inflamed mucosa in patients with active IBD. Treatment with IFX could significantly decrease PLD2 expression in intestinal mucosa in patients with CD. Moreover, blockade of PLD2 with CAY10594 could markedly ameliorate DSS-induced colitis in mice and promote neutrophil migration.Conclusions. PLD2 plays a critical role in the pathogenesis of IBD. Blockade of PLD2 may serve as a new therapeutic approach for treatment of IBD.

scholarly journals Calprotectin: from biomarker to biological function

Gut ◽  
2021 ◽  
pp. gutjnl-2021-324855
Author(s):  
Almina Jukic ◽  
Latifa Bakiri ◽  
Erwin F. Wagner ◽  
Herbert Tilg ◽  
Timon E. Adolph
Keyword(s):  
Dietary Habits ◽  
Biological Function ◽  
Inflammatory Diseases ◽  
Mucosal Inflammation ◽  
Non Invasive ◽  
Mucosal Surfaces ◽  
Organ Systems ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Substantial Morbidity

The incidence of inflammatory bowel diseases (IBD) emerged with Westernisation of dietary habits worldwide. Crohn’s disease and ulcerative colitis are chronic debilitating conditions that afflict individuals with substantial morbidity and challenge healthcare systems across the globe. Since identification and characterisation of calprotectin (CP) in the 1980s, faecal CP emerged as significantly validated, non-invasive biomarker that allows evaluation of gut inflammation. Faecal CP discriminates between inflammatory and non-inflammatory diseases of the gut and portraits the disease course of human IBD. Recent studies revealed insights into biological functions of the CP subunits S100A8 and S100A9 during orchestration of an inflammatory response at mucosal surfaces across organ systems. In this review, we summarise longitudinal evidence for the evolution of CP from biomarker to rheostat of mucosal inflammation and suggest an algorithm for the interpretation of faecal CP in daily clinical practice. We propose that mechanistic insights into the biological function of CP in the gut and beyond may facilitate interpretation of current assays and guide patient-tailored medical therapy in IBD, a concept warranting controlled clinical trials.

scholarly journals Multiple Roles of Myd88 in the Immune Response to the Plague F1-V Vaccine and in Protection against an Aerosol Challenge ofYersinia pestisCO92 in Mice

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Jennifer L. Dankmeyer ◽  
Randy L. Fast ◽  
Christopher K. Cote ◽  
Patricia L. Worsham ◽  
David Fritz ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune System ◽  
Adaptor Protein ◽  
Innate Immune ◽  
Multiple Roles ◽  
Toll Like Receptor ◽  
Wild Type ◽  
Lethal Challenge ◽  
V Protein ◽  
Deficient Mice

The current candidate vaccine againstYersinia pestisinfection consists of two subunit proteins: the capsule protein or F1 protein and the low calcium response V protein or V-antigen. Little is known of the recognition of the vaccine by the host’s innate immune system and how it affects the acquired immune response to the vaccine. Thus, we vaccinated Toll-like receptor (Tlr)2,4, and2/4-double deficient, as well as signal adaptor proteinMyd88-deficient mice. We found that Tlr4 and Myd88 appeared to be required for an optimal immune response to the F1-V vaccine but not Tlr2 when compared to wild-type mice. However, there was a difference between the requirement for Tlr4 and MyD88 in vaccinated animals. When F1-V vaccinatedTlr4mutant (lipopolysaccharide tolerant) andMyd88-deficient mice were challenged by aerosol withY. pestisCO92, all but oneTlr4mutant mice survived the challenge, but no vaccinatedMyd88-deficient mice survived the challenge. Spleens from these latter nonsurviving mice showed thatY. pestiswas not cleared from the infected mice. Our results suggest that MyD88 appears to be important for both an optimal immune response to F1-V and in protection against a lethal challenge ofY. pestisCO92 in F1-V vaccinated mice.

Oral Immune Activation by Disgust and Disease-Related Pictures

2015 ◽  
Vol 29 (3) ◽  
pp. 119-129 ◽  
Author(s):  
Richard J. Stevenson ◽  
Deborah Hodgson ◽  
Megan J. Oaten ◽  
Luba Sominsky ◽  
Mehmet Mahmut ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Innate Immune Response ◽  
Negative Control ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Immune Markers ◽  
Before And After ◽  
Secondary Analyses ◽  
Image Set

Abstract. Both disgust and disease-related images appear able to induce an innate immune response but it is unclear whether these effects are independent or rely upon a common shared factor (e.g., disgust or disease-related cognitions). In this study we directly compared these two inductions using specifically generated sets of images. One set was disease-related but evoked little disgust, while the other set was disgust evoking but with less disease-relatedness. These two image sets were then compared to a third set, a negative control condition. Using a wholly within-subject design, participants viewed one image set per week, and provided saliva samples, before and after each viewing occasion, which were later analyzed for innate immune markers. We found that both the disease related and disgust images, relative to the negative control images, were not able to generate an innate immune response. However, secondary analyses revealed innate immune responses in participants with greater propensity to feel disgust following exposure to disease-related and disgusting images. These findings suggest that disgust images relatively free of disease-related themes, and disease-related images relatively free of disgust may be suboptimal cues for generating an innate immune response. Not only may this explain why disgust propensity mediates these effects, it may also imply a common pathway.

scholarly journals The Role of Enterobacteriaceae in Gut Microbiota Dysbiosis in Inflammatory Bowel Diseases

2021 ◽  
Vol 9 (4) ◽  
pp. 697
Author(s):  
Valerio Baldelli ◽  
Franco Scaldaferri ◽  
Lorenza Putignani ◽  
Federica Del Chierico
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Inflammatory Diseases ◽  
Species Level ◽  
Unknown Etiology ◽  
Gut Dysbiosis ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Symbiotic Microbiota ◽  
Gut Microbiota Dysbiosis

Inflammatory bowel diseases (IBDs) are a group of chronic gastrointestinal inflammatory diseases with unknown etiology. There is a combination of well documented factors in their pathogenesis, including intestinal microbiota dysbiosis. The symbiotic microbiota plays important functions in the host, and the loss of beneficial microbes could favor the expansion of microbial pathobionts. In particular, the bloom of potentially harmful Proteobacteria, especially Enterobacteriaceae, has been described as enhancing the inflammatory response, as observed in IBDs. Herein, we seek to investigate the contribution of Enterobacteriaceae to IBD pathogenesis whilst considering the continuous expansion of the literature and data. Despite the mechanism of their expansion still remaining unclear, their expansion could be correlated with the increase in nitrate and oxygen levels in the inflamed gut and with the bile acid dysmetabolism described in IBD patients. Furthermore, in several Enterobacteriaceae studies conducted at a species level, it has been suggested that some adherent-invasive Escherichia coli (AIEC) play an important role in IBD pathogenesis. Overall, this review highlights the pivotal role played by Enterobacteriaceae in gut dysbiosis associated with IBD pathogenesis and progression.

scholarly journals IL-6 Is Not Absolutely Essential for the Development of a TH17 Immune Response after an Aerosol Infection with Mycobacterium tuberculosis H37rv

Cells ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 9
Author(s):  
Kristina Ritter ◽  
Jan Christian Sodenkamp ◽  
Alexandra Hölscher ◽  
Jochen Behrends ◽  
Christoph Hölscher
Keyword(s):  
Immune Response ◽  
Inflammatory Diseases ◽  
Mycobacterial Infection ◽  
Minor Effect ◽  
Mycobacterium Tuberculosis H37rv ◽  
Th 17 ◽  
Anti Inflammatory ◽  
A Minor ◽  
Aerosol Infection ◽  
Deficient Mice

Anti-inflammatory treatment of chronic inflammatory diseases often increases susceptibility to infectious diseases such as tuberculosis (TB). Since numerous chronic inflammatory and autoimmune diseases are mediated by interleukin (IL)-6-induced T helper (TH) 17 cells, a TH17-directed anti-inflammatory therapy may be preferable to an IL-12-dependent TH1 inhibition in order to avoid reactivation of latent infections. To assess, however, the risk of inhibition of IL-6-dependent TH17-mediated inflammation, we examined the TH17 immune response and the course of experimental TB in IL-6- and T-cell-specific gp130-deficient mice. Our study revealed that the absence of IL-6 or gp130 on T cells has only a minor effect on the development of antigen-specific TH1 and TH17 cells. Importantly, these gene-deficient mice were as capable as wild type mice to control mycobacterial infection. Together, in contrast to its key function for TH17 development in other inflammatory diseases, IL-6 plays an inferior role for the generation of TH17 immune responses during experimental TB.

scholarly journals Innate cell profiles during the acute and convalescent phase of SARS-CoV-2 infection in children

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Melanie R. Neeland ◽  
Samantha Bannister ◽  
Vanessa Clifford ◽  
Kate Dohle ◽  
Kim Mulholland ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Acute Phase ◽  
Innate Immune ◽  
Low Density ◽  
Innate Immune Responses ◽  
Immunological Mechanisms ◽  
Activated Neutrophils ◽  
Classical Monocytes

AbstractChildren have mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) confirmed disease (COVID-19) compared to adults and the immunological mechanisms underlying this difference remain unclear. Here, we report acute and convalescent innate immune responses in 48 children and 70 adults infected with, or exposed to, SARS-CoV-2. We find clinically mild SARS-CoV-2 infection in children is characterised by reduced circulating subsets of monocytes (classical, intermediate, non-classical), dendritic cells and natural killer cells during the acute phase. In contrast, SARS-CoV-2-infected adults show reduced proportions of non-classical monocytes only. We also observe increased proportions of CD63+ activated neutrophils during the acute phase to SARS-CoV-2 in infected children. Children and adults exposed to SARS-CoV-2 but negative on PCR testing display increased proportions of low-density neutrophils that we observe up to 7 weeks post exposure. This study characterises the innate immune response during SARS-CoV-2 infection and household exposure in children.

Clinical Comparison of 99Tcm-Hmpao Labelled Leucocytes and 99Tcm-Nanocolloid in the Detection of Inflammation

1989 ◽  
Vol 30 (6) ◽  
pp. 633-637 ◽  
Author(s):  
M. Vorne ◽  
T. Lantto ◽  
S. Paakkinen ◽  
S. Salo ◽  
I. Soini
Keyword(s):  
Soft Tissue ◽  
Inflammatory Bowel Diseases ◽  
Vascular Graft ◽  
Inflammatory Diseases ◽  
Reliable Information ◽  
Imaging Method ◽  
Joint Diseases ◽  
Labelled Leucocytes ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Forty-five patients with various inflammatory diseases were imaged with 99Tcm-HMPAO labelled leucocytes and 99Tcm-nanocolloid within 7 days. The overall sensitivity of 99Tcm-leucocytes was 97% and that of 99Tcm-nanocolloid 59% and both agents had a 100% specificity. The 99Tcm-leucocyte method showed reliable results in various inflammatory and infectious conditions, and seems suitable as a primary imaging method. On the contrary, 99Tcm-nanocolloid cannot be recommended for use in inflammatory bowel diseases, soft tissue abscesses or prosthetic vascular graft infections. However, 99Tcm-nanocolloid gave reliable information in inflammatory and infectious bone and joint diseases in which it had a 90% sensitivity and 100% specificity. In those lesions the 99Tcm-nanocolloid method may be useful, because it is simple, fast and cheap. Yet, further evaluation is needed.

scholarly journals An In Vitro Assessment of Immunostimulatory Responses to Ten Model Innate Immune Response Modulating Impurities (IIRMIs) and Peptide Drug Product, Teriparatide

Molecules ◽  
2021 ◽  
Vol 26 (24) ◽  
pp. 7461
Author(s):  
Claire K. Holley ◽  
Edward Cedrone ◽  
Duncan Donohue ◽  
Barry W. Neun ◽  
Daniela Verthelyi ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Cytokine Secretion ◽  
Poly I:C ◽  
In Vitro Assays ◽  
Innate Immune Responses ◽  
Vitro Assay

Understanding, predicting, and minimizing the immunogenicity of peptide-based therapeutics are of paramount importance for ensuring the safety and efficacy of these products. The so-called anti-drug antibodies (ADA) may have various clinical consequences, including but not limited to the alteration in the product’s distribution, biological activity, and clearance profiles. The immunogenicity of biotherapeutics can be influenced by immunostimulation triggered by the presence of innate immune response modulating impurities (IIRMIs) inadvertently introduced during the manufacturing process. Herein, we evaluate the applicability of several in vitro assays (i.e., complement activation, leukocyte proliferation, and cytokine secretion) for the screening of innate immune responses induced by ten common IIRMIs (Bacillus subtilis flagellin, FSL-1, zymosan, ODN2006, poly(I:C) HMW, poly(I:C) LMW, CLO75, MDP, ODN2216, and Escherichia coli O111:B4 LPS), and a model biotherapeutic Forteo™ (teriparatide). Our study identifies cytokine secretion from healthy human donor peripheral blood mononuclear cells (PBMC) as a sensitive method for the in vitro monitoring of innate immune responses to individual IIRMIs and teriparatide (TP). We identify signature cytokines, evaluate both broad and narrow multiplex cytokine panels, and discuss how the assay logistics influence the performance of this in vitro assay.

Sign in / Sign up

Export Citation Format

Share Document