scholarly journals The SIRT3 and SIRT6 Promote Prostate Cancer Progression by Inhibiting Necroptosis-Mediated Innate Immune Response

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Weiwei Fu ◽  
Hong Li ◽  
Haiyang Fu ◽  
Shuchao Zhao ◽  
Weiping Shi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Immune Response ◽  
Innate Immune Response ◽  
Cancer Progression ◽  
Nodal Metastasis ◽  
Innate Immune ◽  
Prostate Cancer Progression ◽  
Class Iii ◽  
Expression Levels ◽  
Mrna And Protein Expression

The sirtuins (SIRTs), including seven family members, belong to class III histone deacetylase (HDAC) enzymes, which have been intensively investigated in cancers. Although the function of SIRTs in the cancer immunology is explored, SIRT-specific mechanisms regulating necroptosis-related innate immune response are not clear. In our present study, we found that both the mRNA and protein expression levels of SIRT3 and SIRT6 are significantly increased in the PCa tissues (HR, CI P = 3.30 E − 03 ; HR, CI P = 2.35 E − 08 ; and HR, CI P = 9.20 E − 08 ) and were associated with patients’ Gleason score and nodal metastasis. Furthermore, multivariate analysis showed that the PCa patients with higher expression levels of SIRT3 and SIRT6 had shorter overall survival (OS). Mechanistically, we found that SIRT3 and SIRT6 promote prostate cancer progress by inhibiting RIPK3-mediated necroptosis and innate immune response. Knockdown of both SIRT3 and SIRT6 not only activates TNF-induced necroptosis but also refreshes the corresponding recruitment of macrophages and neutrophils. Overall, our study identified that SIRT3 and SIRT6 are key regulators of necroptosis during prostate cancer progression.

scholarly journals THE MUC5B PROMOTOR POLYMORPHISM ASSOCIATES WITH SEVERE COVID-19

2020 ◽  
Author(s):  
Coline H.M. van Moorsel ◽  
Joanne J van der Vis ◽  
Claudia Benschop ◽  
Henk J.T. Ruven ◽  
Marian Quanjel ◽  
...  
Keyword(s):  
Immune Response ◽  
Lung Disease ◽  
Innate Immune Response ◽  
Survival Data ◽  
Risk Allele ◽  
Promoter Polymorphism ◽  
Innate Immune ◽  
Allele Frequencies ◽  
Expression Levels ◽  
Trade Offs

Background Diversity in response to exposition to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is common and may be related to the innate immune response. The mucin MUC5B is an important component of the innate immune response and expression levels are associated with the MUC5B promoter polymorphism, rs35705950. The high expressing T-allele of rs35705950 is an accepted risk allele for a non-infectious aging lung disease called idiopathic pulmonary fibrosis (IPF). However, given the theory of trade-offs in aging lung disease and the importance of high expression for an adequate immune response, we hypothesize that the T-allele is protective against severe coronavirus disease 2019 (COVID-19). Methods We collected demographics, radiology, survival data and MUC5B rs35705950 allele status for 108 patients requiring hospitalisation for COVID-19 at St Antonius Hospital in The Netherlands. For comparison of allele frequencies and allele carriership with a white control cohort, the patient cohort was divided in a white (n=83) and non-white cohort. Results The patients had a median age of 66 years and consisted predominantly of males (74%) and 23 patients (21%) died. The T-allele frequencies of rs35705950 in white patients was 0.04 which was significantly lower than the T-allele frequency of 0.10 in white controls (p= 0.02). Moreover, comparison of the number of carriers and non-carriers of the T allele showed that only 8.4% of patients carried the T-allele versus 18% of controls (p=0.029; OR= 0.41, CI=0.19-0.94). Conclusions The MUC5B rs35705950 promoter polymorphism associates with COVID-19. The risk allele (T) for IPF is protective against the development of severe COVID-19 disease. This is a further example of a trade-off between optimal expression levels in the respiratory system which associates with aging diseases. However, these results require further investigation.

scholarly journals Angiotensin II AT1 blockade reduces the lipopolysaccharide-induced innate immune response in rat spleen

2009 ◽  
Vol 296 (5) ◽  
pp. R1376-R1384 ◽  
Author(s):  
Enrique Sánchez-Lemus ◽  
Julius Benicky ◽  
Jaroslav Pavel ◽  
Ignacio M. Larrayoz ◽  
Jin Zhou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Inflammatory Response ◽  
Protein Expression ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Bacterial Endotoxin ◽  
Ang Ii ◽  
Tnf Α ◽  
Mrna And Protein Expression

ANG II AT1 receptor blockade reduces inflammation in hypertension. To determine whether ANG II AT1 receptor blockers (ARBs) influence the innate immune inflammatory response in normotensive rats, we studied rat plasma and spleen after a 3-day subcutaneous pretreatment with the ARB candesartan followed by a single dose of the bacterial endotoxin LPS (50 μg/kg ip). Peripheral administration of LPS to rodents produced a generalized inflammatory response with increased release of TNF-α, IL-1β, and IL-6 into the circulation. Candesartan pretreatment reduced the LPS-induced release of TNF-α, IL-1β, and IL-6 into the circulation. The red pulp of rat spleen expressed large numbers of AT1 receptors and the LPS receptors Toll-like receptor 4 and CD14. Candesartan administration significantly blocked AT1 receptors. The ARB reduced the LPS-induced upregulation of CD14 gene expression; expression of TNF-α and IL-6 mRNA and protein; expression of IL-1β and IκB-α mRNA; COX-2 mRNA and protein expression and PGE2 concentration; inducible nitric oxide synthase (iNOS) gene and protein expression and iNOS activity; and Nox2 gene expression and 8-isoprostane levels. In addition, candesartan reduced the CD14 protein expression in saline- and LPS-treated rats. Our results suggest that AT1 receptors are essential for the development of the full innate immune response to bacterial endotoxin. The ARB decreased the general peripheral inflammatory reaction to LPS and partially decreased the inflammatory response in the spleen. An unrestricted innate immune response to the bacterial endotoxin may have deleterious effects for the organism and may lead to development of chronic inflammatory disease. We postulate that ARBs may have therapeutic effects on inflammatory conditions.

scholarly journals Differential Susceptibility and Innate Immune Response of Aedes aegypti and Aedes albopictus to the Haitian Strain of the Mayaro Virus

Viruses ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 924 ◽  
Author(s):  
Diop ◽  
Alout ◽  
Diagne ◽  
Bengue ◽  
Baronti ◽  
...  
Keyword(s):  
Immune Response ◽  
Aedes Aegypti ◽  
Innate Immune Response ◽  
Aedes Albopictus ◽  
Serine Proteases ◽  
Early Stage ◽  
Mosquito Species ◽  
Innate Immune ◽  
Expression Levels ◽  
Npc1 Gene

Mayaro (MAYV) is an emerging arthropod-borne virus belonging to the Alphavirus genus of the Togaviridae family. Although forest-dwelling Haemagogus mosquitoes have been considered as its main vector, the virus has also been detected in circulating Aedes ssp mosquitoes. Here we assess the susceptibility of Aedes aegypti and Aedes albopictus to infection with MAYV and their innate immune response at an early stage of infection. Aedes albopictus was more susceptible to infection with MAYV than Ae. aegypti. Analysis of transcript levels of twenty immunity-related genes by real-time PCR in the midgut of both mosquitoes infected with MAYV revealed increased expression of several immune genes, including CLIP-domain serine proteases, the anti-microbial peptides defensin A, E, cecropin E, and the virus inducible gene. The regulation of certain genes appeared to be Aedes species-dependent. Infection of Ae. aegypti with MAYV resulted in increased levels of myeloid differentiation2-related lipid recognition protein (ML26A) transcripts, as compared to Ae. albopictus. Increased expression levels of thio-ester-containing protein 22 (TEP22) and Niemann–Pick type C1 (NPC1) gene transcripts were observed in infected Ae. albopictus, but not Ae. aegypti. The differences in these gene expression levels during MAYV infection could explain the variation in susceptibility observed in both mosquito species.

DIFFERENCES IN THE EXPRESSION OF INNATE IMMUNE RESPONSE-MODULATING GENES IN BLOOD MONOCYTES BETWEEN SUBCLINICALLY PORCINE CIRCOVIRUS TYPE 2 (PCV2)-INFECTED AND PCV2-FREE PIGS PRIOR TO AND AFTER LIPOPOLYSACCHARIDE STIMULATIONIN VITRO

2014 ◽  
Vol 40 (01) ◽  
pp. 37-48
Author(s):  
Yi-Chieh Tsai ◽  
Chian-Ren Jeng ◽  
Chih-Cheng Chang ◽  
Shih-Hsuan Hsiao ◽  
Hui-Wen Chang ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Secondary Infection ◽  
Porcine Circovirus Type ◽  
Innate Immune ◽  
Porcine Circovirus ◽  
Blood Monocytes ◽  
Expression Levels ◽  
Tnf Α

The objective of the present study was to characterize and compare the differences in gene expression associated with innate immune response of blood monocytes (Mos) between healthy subclinically PCV2-infected and PCV2-free pigs prior to and after lipopolysaccharide (LPS) stimulation in vitro by relative quantitative real-time PCR (q-rt-PCR). Genes coding for 24 innate molecules, including toll-like receptors (TLRs), interferon-regulatory factors (IRFs), nuclear factor kappa-light chain-enhancer of activated B cells (NF-κB) and pro-inflammatory cytokines were evaluated. When compared with PCV2-free pigs, Mos from subclinically PCV2-infected pigs showed significantly lower mRNA expression levels in TLR-9, IRF-3, IRF-6, IRF-7, IL-6, IL-12p35, IL-12p40 and IFN-α under no further stimulation. Following LPS stimulation in vitro, a broad and/or obvious reduction in TLRs, IRFs, IL-12 and IFN-α along with increase in IL-1α, IL-6, IL-8, IL-10 and/or TNF-α were seen in both PCV2-free and subclinically PCV2-infected pigs; when compared with PCV2-free pigs, the subclinically PCV2-infected pigs had significantly higher expression levels in TLR-10 and IRF-1 but lower expression levels in IRF-6, IL-1α and IL-12p40. On the contrary, the expression level of NF-κB was consistently higher in subclinically PCV2-infected pigs than in PCV2-free pigs with or without LPS stimulation. The changes seen in the present study suggest that the subclinically PCV2-infected pigs may look healthy clinically, but their innate immunity has become dis-regulated or is in an improper status. The adverse condition may become even worse when exposed to certain bacterial products such as endotoxin. Such alterations in the innate immune system may make the subclinically PCV2-infected pigs more vulnerable to the secondary infection and subsequent PCV2-associated disease development.

scholarly journals Metabolic Hormones Modulate Macrophage Inflammatory Responses

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4661
Author(s):  
Matthew J. Batty ◽  
Gwladys Chabrier ◽  
Alanah Sheridan ◽  
Matthew C. Gage
Keyword(s):  
Immune Response ◽  
Inflammatory Response ◽  
Innate Immune Response ◽  
Cancer Progression ◽  
Metabolic Diseases ◽  
Inflammatory Responses ◽  
Innate Immune ◽  
Metabolic Hormones ◽  
Cancer Types

Macrophages are phagocytotic leukocytes that play an important role in the innate immune response and have established roles in metabolic diseases and cancer progression. Increased adiposity in obese individuals leads to dysregulation of many hormones including those whose functions are to coordinate metabolism. Recent evidence suggests additional roles of these metabolic hormones in modulating macrophage inflammatory responses. In this review, we highlight key metabolic hormones and summarise their influence on the inflammatory response of macrophages and consider how, in turn, these hormones may influence the development of different cancer types through the modulation of macrophage functions.

scholarly journals Prostaglandin E2 Inhibits Prostate Cancer Progression by Countervailing Tumor Microenvironment-Induced Impairment of Dendritic Cell Migration through LXRα/CCR7 Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Kuang Youlin ◽  
He Weiyang ◽  
Liang Simin ◽  
Gou Xin
Keyword(s):  
Prostate Cancer ◽  
Immune Response ◽  
Dendritic Cells ◽  
Cell Migration ◽  
Dendritic Cell ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Prostaglandin E ◽  
Prostate Cancer Progression ◽  
Dendritic Cell Migration

Migration and homing of dendritic cells (DCs) to lymphoid organs are quite crucial for T cell-induced immune response against tumor. However, tumor microenvironment can make some tumor cells escape immune response by impairing DC migration. Prostaglandin E2 (PGE2) plays important roles in initiating and terminating inflammatory responses. In this study, we investigated whether PGE2 could inhibit murine prostate cancer progression by countervailing tumor microenvironment-induced impairment of dendritic cell migration. We found that murine prostate cancer cell line RM-1-conditioned medium impaired chemotactic movement of marrow-derived DCs and splenic cDCs toward CC chemokine receptor-7 (CCR7) ligand CCL19 in vitro and migration to draining lymph gland in vivo. Meanwhile, it also induced LXRα activation and CCR7 inhibition on maturing DCs. However, the treatment of PGE2 rescued this impairment of DC migration with upregulation of CCR7 and inhibition of LXRα. Further, it was observed that PGE2 also increased MMP9 expression and activated Notch1 signaling on DCs. In RM-1-bearing mouse model, PGE2 treatment was identified to inhibit tumor growth and induce more tumor-infiltrating T cells and CD11c dendritic cells in tumor sites. Therefore, our findings may demonstrate a new perspective for therapeutic interventions on prostate cancer immunoescape.

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