scholarly journals Campylobacter jejuni-Induced Cytokine Responses in Avian Cells

2005 ◽  
Vol 73 (4) ◽  
pp. 2094-2100 ◽  
Author(s):  
Chris K. Smith ◽  
Pete Kaiser ◽  
Lisa Rothwell ◽  
Tom Humphrey ◽  
Paul A. Barrow ◽  
...  
Keyword(s):  
Campylobacter Jejuni ◽  
Proinflammatory Cytokines ◽  
Disease Process ◽  
Avian Host ◽  
Macrophage Cell ◽  
Proinflammatory Response ◽  
Cytokines And Chemokines ◽  
Cytokine Responses ◽  
Chick Kidney

ABSTRACT Campylobacter jejuni is a major cause of human inflammatory enteritis. During the course of human disease numerous proinflammatory cytokines are produced. Little is known, however, about the cytokine responses produced during the interaction of this bacterium with the avian host. Campylobacter has been considered a commensal of the avian host. Any differences in innate responses to this pathogen between the human and avian hosts should lead to a greater understanding of the disease process in humans. We have demonstrated expression of proinflammatory cytokines and chemokines in response to Campylobacter infection in avian primary chick kidney cells and the avian macrophage cell line HD11. The data indicate that Campylobacter can stimulate the avian host in a proinflammatory manner. The data strongly suggest that the lack of pathology in vivo is not due to an inability of Campylobacter to stimulate a proinflammatory response from avian cells.

scholarly journals Invasive Phenotype of Candida albicans Affects the Host Proinflammatory Response to Infection

2005 ◽  
Vol 73 (8) ◽  
pp. 4588-4595 ◽  
Author(s):  
C. C. Villar ◽  
H. Kashleva ◽  
A. P. Mitchell ◽  
A. Dongari-Bagtzoglou
Keyword(s):  
Endothelial Cells ◽  
Candida Albicans ◽  
Proinflammatory Cytokines ◽  
Proinflammatory Cytokine ◽  
Inflammatory Responses ◽  
Gene Knockout ◽  
Critical Role ◽  
Host Cells ◽  
Proinflammatory Response ◽  
Cytokine Responses

ABSTRACT Candida albicans is a major opportunistic pathogen in immunocompromised patients. Production of proinflammatory cytokines by host cells in response to C. albicans plays a critical role in the activation of immune cells and final clearance of the organism. Invasion of host cells and tissues is considered one of the virulence attributes of this organism. The purpose of this study was to investigate whether the ability of C. albicans to invade host cells and tissues affects the proinflammatory cytokine responses by epithelial and endothelial cells. In this study we used the invasion-deficient RIM101 gene knockout strain DAY25, the highly invasive strain SC5314, and highly invasive RIM101-complemented strain DAY44 to compare the proinflammatory cytokine responses by oral epithelial or endothelial cells. Using a high-throughput approach, we found both qualitative and quantitative differences in the overall inflammatory responses to C. albicans strains with different invasive potentials. Overall, the highly invasive strains triggered higher levels of proinflammatory cytokines in host cells than the invasion-deficient mutant triggered. Significant differences compared to the attenuated mutant were noted in interleukin-1α (IL-1α), IL-6, IL-8, and tumor necrosis factor alpha in epithelial cells and in IL-6, growth-related oncogene, IL-8, monocyte chemoattractant protein 1 (MCP-1), MCP-2, and granulocyte colony-stimulating factor in endothelial cells. Our results indicate that invasion of host cells and tissues by C. albicans enhances the host proinflammatory response to infection.

Activation of the MKK3-p38-MK2-ZFP36 axis by coronavirus infection restricts the upregulation of AU-rich element-containing transcripts in proinflammatory response

2022 ◽  
Author(s):  
Shumin Li ◽  
Siying Liu ◽  
Rui Ai Chen ◽  
Mei Huang ◽  
To Sing Fung ◽  
...  
Keyword(s):  
Map Kinase ◽  
Proinflammatory Cytokines ◽  
Binding Protein ◽  
Regulatory Role ◽  
Proinflammatory Response ◽  
Cytokines And Chemokines ◽  
Coronavirus Infection ◽  
Anti Inflammatory ◽  
Coronavirus Infections ◽  
In Cells

Coronavirus infections induce the expression of multiple proinflammatory cytokines and chemokines. We have previously shown that in cells infected with gammacoronavirus infectious bronchitis virus (IBV), interleukin 6 (IL-6) and IL-8 were drastically upregulated, and the MAP kinase p38 and the integrated stress response pathways were implicated in this process. In this study, we report that coronavirus infection activates a negative regulatory loop that restricts the upregulation of a number of proinflammatory genes. As revealed by the initial transcriptomic and subsequent validation analyses, the anti-inflammatory adenine-uridine (AU)-rich element (ARE)-binding protein, Zinc finger protein 36 (ZFP36) and its related family members were upregulated in cells infected with IBV and three other coronaviruses, alphacoronaviruses porcine epidemic diarrhea virus (PEDV) and human coronavirus 229E (HCoV-229E), and betacoronavirus HCoV-OC43, respectively. Characterization of the functional roles of ZFP36 during IBV infection demonstrated that ZFP36 promoted the degradation of transcripts coding for IL-6, IL-8, dual-specificity phosphatase 1 (DUSP1), prostaglandin-endoperoxide synthase 2 (PTGS2) and TNF-α-induced protein 3 (TNFAIP3), through binding to AREs in these transcripts. Consistently, knockdown and inhibition of JNK and p38 kinase activities reduced the expression of ZFP36, as well as the expression of IL-6 and IL-8. On the contrary, overexpression of mitogen-activated protein kinase kinase 3 (MKK3) and MAPKAP kinase-2 (MK2), the upstream and downstream kinases of p38, respectively, increased the expression of ZFP36 and decreased the expression of IL-8. Taken together, this study reveals an important regulatory role of the MKK3-p38-MK2-ZFP36 axis in coronavirus infection-induced proinflammatory response. Importance Excessive and uncontrolled induction and release of proinflammatory cytokines and chemokines, the so-called cytokine release syndrome (CRS), would cause life-threatening complications and multiple organ failure in severe coronavirus infections, including severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and COVID-19. This study reveals that coronavirus infection also induces the expression of ZFP36, an anti-inflammatory ARE-binding protein, promoting the degradation of ARE-containing transcripts coding for IL-6 and IL-8 as well as a number of other proteins related to inflammatory response. Furthermore, the p38 MAP kinase, its upstream kinase MKK3 and downstream kinase MK2 were shown to play a regulatory role in upregulation of ZFP36 during coronavirus infection cycles. This MKK3-p38-MK2-ZFP36 axis would constitute a potential therapeutic target for severe coronavirus infections.

scholarly journals Production of Proinflammatory Cytokines and Chemokines During Neuroinflammation: Novel Roles for Estrogen Receptors α and β

Endocrinology ◽  
2010 ◽  
Vol 151 (10) ◽  
pp. 4916-4925 ◽  
Author(s):  
Candice M. Brown ◽  
Tara A. Mulcahey ◽  
Nicole C. Filipek ◽  
Phyllis M. Wise
Keyword(s):  
Estrogen Receptors ◽  
Proinflammatory Cytokines ◽  
Neurological Disorders ◽  
Chemokine Production ◽  
Neuroinflammatory Response ◽  
Cytokines And Chemokines ◽  
The Central Nervous System ◽  
Mice Brain ◽  
Estradiol 17Β

Neuroinflammation is a common feature of many neurological disorders, and it is often accompanied by the release of proinflammatory cytokines and chemokines. Estradiol-17β (E2) exhibits antiinflammatory properties, including the suppression of proinflammatory cytokines, in the central nervous system. However, the mechanisms employed by E2 and the role(s) of estrogen receptors (ERs) ERα and ERβ are unclear. To investigate these mechanisms, we employed an in vivo lipopolysaccharide (LPS) model of systemic inflammation in ovariectomized (OVX) and OVX and E2-treated (OVX+E2) mice. Brain levels of proinflammatory cytokines (IL-1β, IL-6, and IL-12p40) and chemokines (CCL2/MCP-1, CCL3/MIP-1α, CCL5/RANTES, and CXCL1/KC) were quantified in mice at 0 (sham), 3, 6, 12, and 24 h after infection using multiplex protein analysis. E2 treatment inhibited LPS-induced increases in all cytokines. In contrast, E2 treatment only suppressed CCL/RANTES chemokine concentrations. To determine whether ERα and ERβ regulate brain cytokine and chemokine levels, parallel experiments were conducted using ERα knockout and ERβ knockout mice. Our results revealed that both ERα and ERβ regulated proinflammatory cytokine and chemokine production through E2-dependent and E2-independent mechanisms. To assess whether breakdown of the blood-brain barrier is an additional target of E2 against LPS-induced neuroinflammation, we measured Evan’s blue extravasation and identified distinct roles for ERα and ERβ. Taken together, these studies identify a dramatic cytokine- and chemokine-mediated neuroinflammatory response that is regulated through ERα- and ERβ-mediated ligand-dependent and ligand-independent mechanisms.

MicroRNA-155 promotes atherosclerosis-signaling pathway through targeting gene/SOCS1 and IRAKM

2014 ◽  
Vol 2 (4) ◽  
pp. 260-269
Keyword(s):  
Immune Response ◽  
Proinflammatory Cytokines ◽  
Proinflammatory Cytokine ◽  
Target Genes ◽  
Atherogenic Diet ◽  
Mice Model ◽  
Proinflammatory Response ◽  
Molecular Control

MiR-155 plays a role in the regulates various aspects of innate and adaptive immune response, physiological and pathological processes. Exogenous molecular control in vivo of miR-155 expression may inhibit malignant growth, viral infections, and attenuate the progression of cardiovascular diseases. Up-regulation of proinflammatory cytokines plays a central role in atherosclerosis. In this study, we investigated the role of miR-155 in regulating proinflammatory response in atherosclerosis. Hyperlipidemic C57BL/6 male mice model were fed with atherogenic-diet for 12-weeks. MiR-155 positively regulates proinflammatory cytokines and we found increased TNFα, IL-1b, IL-6 mRNA and NF-kB in hyperlipidemic mice. Furthermore, increased miR-155 levels are correlated with proinflammatory cytokine expression in hyperlipidemic mice. To understand the mechanism by which miR-155 regulates proinflammatory cytokines in atherosclerosis, we evaluated the miR-155 target genes SOCS1 and IRAKM. We found increased miR-155 and decreased expression of SOCS1 and IRAKM in hyperlipidemic mice. Interestingly inhibition of miR-155 by using a specific miR-155 silencing, inhibited proinflammatory cytokine in hyperlipidemic mice, suggesting a role of miR-155 in immune response regulation. Based on these observations, we conclude that miR-155 modulates proinflammatory response in hyperlipidemic mice via regulation of SOCS1 and IRAKM expression. Thus, modulation of miR-155 could be a strategy to regulate atherogenic diet-induced atherosclerosis where proinflammatory cytokine plays significant role in disease progression.

scholarly journals Two-Component Signal Transduction System VraSR Contributes to Neuroinflammation in Streptococcus Suis Meningitis

2021 ◽  
Author(s):  
Beibei Dou ◽  
Xia Yang ◽  
Fengming Yang ◽  
Kang Yan ◽  
Wei Peng ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Proinflammatory Cytokines ◽  
Regulatory System ◽  
Streptococcus Suis ◽  
Wild Type ◽  
Signal Transduction System ◽  
Cytokines And Chemokines ◽  
Two Component ◽  
Two Component Signal Transduction

Abstract Background: Streptococcus suis (S. suis) is an important zoonotic pathogen that can cause high morbidity and mortality in both humans and swine. As the most important life-threatening infection of the central nervous system (CNS), meningitis is an important symptom of S. suis infection. The VraSR is a critical two-component signal transduction system that affects S. suis ability to resist against host innate immune system and promotes the ability of S. suis to adhere to hBMEC. Whether and how VraSR contributes to the development of S. suis meningitis are currently unknown.Methods: The in vivo colonization, in vivo BBB permeability, histopathological examination and immunohistochemistry were applied to compare and characterize the degree of destruction of brain tissue in response to wild type SC19 and mutant ΔvraSR. Western blotting and real-time PCR were combined to identify the breakdown of tight junction proteins (TJ proteins). The secretion of proinflammatory cytokines and chemokines in the serum were detected on a BD FACSVerse flow cytometer.Results: We found an important role of VraSR regulatory system in S. suis SC19-induced meningitis. A mouse infection model demonstrated that ΔvraSR had significantly attenuated inflammatory lesions in the brain tissues compared with wild-type S. suis. In vitro, we characterized that SC19 could increase the blood-brain barrier (BBB) permeability through downregulating the TJ proteins compared with mutant ΔvraSR. Moreover, we found significant generation of proinflammatory cytokines and chemokines in the serum including IL-6, TNF-α, MCP-1, and IL-12p70 compared with ΔvraSR infected mice.Conclusions: For the first time, our work investigated the VraSR regulatory system of S. suis played an important role in streptococcal meningitis and revealed VraSR to be an important contributor to the disruption of TJ proteins. Characterization of these BBB disruption will facilitate further study of meningitis mechanisms in humans, thereby offering the development of novel preventative and therapeutic strategies against infection with S. suis.

Induction of chicken cytokine responses in vivo and in vitro by lipooligosaccharide of Campylobacter jejuni HS:10

2013 ◽  
Vol 164 (1-2) ◽  
pp. 122-130 ◽  
Author(s):  
Neda Barjesteh ◽  
Douglas C. Hodgins ◽  
Michael St. Paul ◽  
Wanderley M. Quinteiro-Filho ◽  
Christina DePass ◽  
...  
Keyword(s):  
Campylobacter Jejuni ◽  
Cytokine Responses

scholarly journals Inhibition of Notch signalling ameliorates experimental inflammatory arthritis

2013 ◽  
Vol 74 (1) ◽  
pp. 267-274 ◽  
Author(s):  
Jong-Sung Park ◽  
Seol-Hee Kim ◽  
Kwangmeyung Kim ◽  
Cheng-Hao Jin ◽  
Ki Young Choi ◽  
...  
Keyword(s):  
Proinflammatory Cytokines ◽  
Inflammatory Arthritis ◽  
Near Infrared ◽  
Joint Destruction ◽  
Disease Onset ◽  
Disease Process ◽  
Neutrophil Infiltration ◽  
Notch Signalling ◽  
Pharmacological Inhibition

ObjectiveTo test the hypothesis that Notch signalling plays a role in the pathogenesis of rheumatoid arthritis (RA) and to determine whether pharmacological inhibition of Notch signalling with γ-secretase inhibitors can ameliorate the RA disease process in an animal model.MethodsCollagen-induced arthritis was induced in C57BL/6 or Notch antisense transgenic mice by immunisation with chicken type II collagen (CII). C57BL/6 mice were administered with different doses of inhibitors of γ-secretase, an enzyme required for Notch activation, at disease onset or after onset of symptoms. Severity of arthritis was monitored by clinical and histological scores, and in vivo non-invasive near-infrared fluorescence (NIRF) images. Micro-CT was used to confirm joint destruction. The levels of CII antibodies and cytokines in serum were determined by ELISA and bead-based cytokine assay. The expression levels of cytokines were studied by quantitative PCR in rheumatoid synovial fibroblasts.ResultsThe data show that Notch signalling stimulates synoviocytes and accelerates their production of proinflammatory cytokines and immune responses involving the upregulation of IgG1 and IgG2a. Pharmacological inhibition of γ-secretase and antisense-mediated knockdown of Notch attenuates the severity of inflammatory arthritis, including arthritis indices, paw thickness, tissue damage and neutrophil infiltration, and reduces the levels of active NF-κB, ICAM-1, proinflammatory cytokines and matrix metalloproteinase-3 activity in the mouse model of RA.ConclusionsThese results suggest that Notch is involved in the pathogenesis of RA and that inhibition of Notch signalling is a novel approach for treating RA.

scholarly journals Rapid Expression of Chemokines and Proinflammatory Cytokines in Newly Hatched Chickens Infected with Salmonella enterica Serovar Typhimurium

2004 ◽  
Vol 72 (4) ◽  
pp. 2152-2159 ◽  
Author(s):  
G. S. K. Withanage ◽  
Pete Kaiser ◽  
Paul Wigley ◽  
Claire Powers ◽  
Pietro Mastroeni ◽  
...  
Keyword(s):  
Proinflammatory Cytokines ◽  
Salmonella Enterica ◽  
Bacterial Colonization ◽  
Oral Infection ◽  
Poultry Meat ◽  
Exact Nature ◽  
Cytokines And Chemokines ◽  
Inflammatory Protein ◽  
Serovar Typhimurium

ABSTRACT Poultry meat and eggs contaminated with Salmonella enterica serovar Enteritidis or Salmonella enterica serovar Typhimurium are common sources of acute gastroenteritis in humans. However, the exact nature of the immune mechanisms protective against Salmonella infection in chickens has not been characterized at the molecular level. In the present study, bacterial colonization, development of pathological lesions, and proinflammatory cytokine and chemokine gene expression were investigated in the liver, spleen, jejunum, ileum, and cecal tonsils in newly hatched chickens 6, 12, 24, and 48 h after oral infection with Salmonella serovar Typhimurium. Very high bacterial counts were found in the ileum and cecal contents throughout the experiment, whereas Salmonella started to appear in the liver only from 24 h postinfection. Large numbers of heterophils, equivalent to neutrophils in mammals, and inflammatory edema could be seen in the lamina propria of the intestinal villi and in the liver. Interleukin 8 (IL-8), K60 (a CXC chemokine), macrophage inflammatory protein 1 β, and IL-1β levels were significantly upregulated in the intestinal tissues and in the livers of the infected birds. However, the spleens of the infected birds show little or no change in the expression levels of these cytokines and chemokines. Increased expression of the proinflammatory cytokines and chemokines (up to several hundred-fold) correlated with the presence of inflammatory signs in those tissues. This is the first description of in vivo expression of chemokines and proinflammatory cytokines in response to oral infection with Salmonella in newly hatched chickens.

scholarly journals Protein PGLYRP1/Tag7 Peptides Decrease the Proinflammatory Response in Human Blood Cells and Mouse Model of Diffuse Alveolar Damage of Lung through Blockage of the TREM-1 and TNFR1 Receptors

2021 ◽  
Vol 22 (20) ◽  
pp. 11213
Author(s):  
Tatiana N. Sharapova ◽  
Elena A. Romanova ◽  
Aleksandr S. Chernov ◽  
Alexey N. Minakov ◽  
Vitaly A. Kazakov ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Mouse Model ◽  
Proinflammatory Cytokines ◽  
Mononuclear Cells ◽  
Diffuse Alveolar Damage ◽  
Proinflammatory Response ◽  
Peripheral Blood Mononuclear ◽  
Terminal Fragment

Infection caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2) in many cases is accompanied by the release of a large amount of proinflammatory cytokines in an event known as “cytokine storm”, which is associated with severe coronavirus disease 2019 (COVID-19) cases and high mortality. The excessive production of proinflammatory cytokines is linked, inter alia, to the enhanced activity of receptors capable of recognizing the conservative regions of pathogens and cell debris, namely TLRs, TREM-1 and TNFR1. Here we report that peptides derived from innate immunity protein Tag7 inhibit activation of TREM-1 and TNFR1 receptors during acute inflammation. Peptides from the N-terminal fragment of Tag7 bind only to TREM-1, while peptides from the C-terminal fragment interact solely with TNFR1. Selected peptides are capable of inhibiting the production of proinflammatory cytokines both in peripheral blood mononuclear cells (PBMCs) from healthy donors and in vivo in the mouse model of acute lung injury (ALI) by diffuse alveolar damage (DAD). Treatment with peptides significantly decreases the infiltration of mononuclear cells to lungs in animals with DAD. Our findings suggest that Tag7-derived peptides might be beneficial in terms of the therapy or prevention of acute lung injury, e.g., for treating COVID-19 patients with severe pulmonary lesions.

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