scholarly journals A Co-Culture Model of IPEC-J2 and Swine PBMC to Study the Responsiveness of Intestinal Epithelial Cells: The Regulatory Effect of Arginine Deprivation

Animals ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 2756
Author(s):  
Roberta Saleri ◽  
Paolo Borghetti ◽  
Francesca Ravanetti ◽  
Melania Andrani ◽  
Valeria Cavalli ◽  
...  

Arginine is a semi-essential amino acid, supplementation with which induces a reduction of intestinal damage and an improvement of intestinal immunity in weaned piglets, but the mechanism is not yet entirely clear. The aim of this study was to characterise a co-culture model by measuring changes in gene expression over time (24 and 48 h) in intestinal IPEC-J2 cells in the presence of immune cells activated with phytohemagglutinin and, consequently, to assess the effectiveness of arginine deprivation or supplementation in modulating the expression of certain cytokines related to the regulation of intestinal cells’ function. The main results show the crucial role of arginine in the viability/proliferation of intestinal cells evaluated by an MTT assay, and in the positive regulation of the expression of pro-inflammatory (TNF-α, IL-1α, IL-6, IL-8) and anti-inflammatory (TGF-β) cytokines. This experimental model could be important for analysing and clarifying the role of nutritional conditions in intestinal immune cells’ functionality and reactivity in pigs as well as the mechanisms of the intestinal defence system. Among the potential applications of our in vitro model of interaction between IEC and the immune system there is the possibility of studying the effect of feed additives to improve animal health and production.

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Phillips-Farfán Bryan ◽  
Carvajal Karla ◽  
Medina-Torres Edgar Alejandro ◽  
Espinosa-Padilla Sara Elva ◽  
Fabrias Gemma ◽  
...  

Inflammatory bowel disease (IBD) describes different illnesses characterized by chronic inflammation of the gastrointestinal tract. Although the pathogenic mechanisms leading to IBD are poorly understood, immune system disturbances likely underlie its development. Sphingolipids (SLs) have been identified as important players and promising therapeutic targets to control inflammation in IBD. Interestingly, it seems that microorganisms of the normal gut microbiota and probiotics are involved in sphingolipid function. However, there is a great need to investigate the role of SLs as intermediates in the crosstalk between intestinal immunity and microorganisms. This review focuses on recent investigations that describe some mechanisms involved in the regulation of cytokine profiles by SLs. We also describe the importance of gut microbiota in providing signaling molecules that favor the communication between resident bacteria and intestinal cells. This, in turn, modulates the immune response in the bowel and likely in other peripheral organs. The potential of SLs and gut microbiota as targets or therapeutic agents for IBD is also discussed.


Metabolites ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 406
Author(s):  
Clément Caffaratti ◽  
Caroline Plazy ◽  
Geoffroy Mery ◽  
Abdoul-Razak Tidjani ◽  
Federica Fiorini ◽  
...  

Trillions of microorganisms, termed the “microbiota”, reside in the mammalian gastrointestinal tract, and collectively participate in regulating the host phenotype. It is now clear that the gut microbiota, metabolites, and intestinal immune function are correlated, and that alterations of the complex and dynamic host-microbiota interactions can have deep consequences for host health. However, the mechanisms by which the immune system regulates the microbiota and by which the microbiota shapes host immunity are still not fully understood. This article discusses the contribution of metabolites in the crosstalk between gut microbiota and immune cells. The identification of key metabolites having a causal effect on immune responses and of the mechanisms involved can contribute to a deeper insight into host-microorganism relationships. This will allow a better understanding of the correlation between dysbiosis, microbial-based dysmetabolism, and pathogenesis, thus creating opportunities to develop microbiota-based therapeutics to improve human health. In particular, we systematically review the role of soluble and membrane-bound microbial metabolites in modulating host immunity in the gut, and of immune cells-derived metabolites affecting the microbiota, while discussing evidence of the bidirectional impact of this crosstalk. Furthermore, we discuss the potential strategies to hear the sound of such metabolite-mediated crosstalk.


2020 ◽  
Vol 21 (15) ◽  
pp. 1558-1565
Author(s):  
Matteo Santoni ◽  
Francesco Massari ◽  
Liang Cheng ◽  
Alessia Cimadamore ◽  
Marina Scarpelli ◽  
...  

The carcinogenesis of prostate cancer (PCa) results from a complex series of events. Chronic inflammation and infections are crucial in this context. Infiltrating M2 type macrophages, as well as neutrophils and T lymphocytes, contribute to PCa development, progression and response to therapy. The preliminary findings on the efficacy of immunotherapy in patients with PCa were not encouraging. However, a series of studies investigating anti-PD-L1 agents such as Atezolizumab, Avelumab and Durvalumab used alone or in combination with other immunotherapies, chemotherapy or locoregional approaches are in course in this tumor. In this review, we illustrate the role of immune cells and PD-L1 expression during PCa carcinogenesis and progression, with a focus on ongoing clinical trials on anti-PD-L1 agents in this context.


Forests ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 25
Author(s):  
László Somay ◽  
Viktor Szigeti ◽  
Gergely Boros ◽  
Réka Ádám ◽  
András Báldi

Wood pastures are home to a variety of species, including the dung beetle. Dung beetles are an important functional group in decomposition. Specifically, in terms of livestock manure, they not only contribute to nutrient cycling but are key players in supporting human and animal health. Dung beetles, however, are declining in population, and urgent recommendations are needed to reverse this trend. Recommendations need to be based on solid evidence and specific habitats. Herein, we aimed to investigate the role of an intermediate habitat type between forests and pastures. Wood pastures are key areas for dung beetle conservation. For this reason, we compared dung beetle assemblages among forests, wood pastures, and grasslands. We complemented this with studies on the effects of dung type and season at three Hungarian locations. Pitfall traps baited with cattle, sheep, or horse dung were used in forests, wood pastures, and pasture habitats in spring, summer, and autumn. Dung beetle assemblages of wood pastures showed transient characteristics between forests and pastures regarding their abundance, species richness, Shannon diversity, assemblage composition, and indicator species. We identified a strong effect of season and a weak of dung type. Assemblage composition proved to be the most sensitive measure of differences among habitats. The conservation of dung beetles, and the decomposition services they provide, need continuous livestock grazing to provide fresh dung, as well as the maintenance of wood pastures where dung beetle assemblages typical of forests and pastures can both survive.


Inflammation ◽  
2021 ◽  
Author(s):  
Yi-jin Wu ◽  
Li Wang ◽  
Chao-fan Ji ◽  
Shao-fei Gu ◽  
Qin Yin ◽  
...  

2021 ◽  
Author(s):  
Yu-Huan Chen ◽  
Jenn-Yeu Shin ◽  
Hsiu-Mei Wei ◽  
Chi-Chen Lin ◽  
Linda Chia-Hui Yu ◽  
...  

A fungal immunomodulatory protein Ling Zhi-8 (LZ-8) isolated from Ganoderma lucidum (GL) regulates immune cells and inhibits tumor growth; however, the role of LZ-8 in intestinal epithelial cells (IECs) is...


Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2554
Author(s):  
Marc Micó-Carnero ◽  
Araní Casillas-Ramírez ◽  
Albert Caballeria-Casals ◽  
Carlos Rojano-Alfonso ◽  
Alfredo Sánchez-González ◽  
...  

Herein, we investigate whether: (1) the administration of glucose or a lipid emulsion is useful in liver transplantation (LT) using steatotic (induced genetically or nutritionally) or non-steatotic livers from donors after brain death (DBDs); and (2) any such benefits are due to reductions in intestinal damage and consequently to gut microbiota preservation. In recipients from DBDs, we show increased hepatic damage and failure in the maintenance of ATP, glycogen, phospholipid and growth factor (HGF, IGF1 and VEGFA) levels, compared to recipients from non-DBDs. In recipients of non-steatotic grafts from DBDs, the administration of glucose or lipids did not protect against hepatic damage. This was associated with unchanged ATP, glycogen, phospholipid and growth factor levels. However, the administration of lipids in steatotic grafts from DBDs protected against damage and ATP and glycogen drop and increased phospholipid levels. This was associated with increases in growth factors. In all recipients from DBDs, intestinal inflammation and damage (evaluated by LPS, vascular permeability, mucosal damage, TLR4, TNF, IL1, IL-10, MPO, MDA and edema formation) was not shown. In such cases, potential changes in gut microbiota would not be relevant since neither inflammation nor damage was evidenced in the intestine following LT in any of the groups evaluated. In conclusion, lipid treatment is the preferable nutritional support to protect against hepatic damage in steatotic LT from DBDs; the benefits were independent of alterations in the recipient intestine.


2021 ◽  
Vol 7 (8) ◽  
pp. eabc2331 ◽  
Author(s):  
Jose M. Ayuso ◽  
Shujah Rehman ◽  
Maria Virumbrales-Munoz ◽  
Patrick H. McMinn ◽  
Peter Geiger ◽  
...  

Solid tumors generate a suppressive environment that imposes an overwhelming burden on the immune system. Nutrient depletion, waste product accumulation, hypoxia, and pH acidification severely compromise the capacity of effector immune cells such as T and natural killer (NK) cells to destroy cancer cells. However, the specific molecular mechanisms driving immune suppression, as well as the capacity of immune cells to adapt to the suppressive environment, are not completely understood. Thus, here, we used an in vitro microfluidic tumor-on-a-chip platform to evaluate how NK cells respond to the tumor-induced suppressive environment. The results demonstrated that the suppressive environment created by the tumor gradually eroded NK cell cytotoxic capacity, leading to compromised NK cell surveillance and tumor tolerance. Further, NK cell exhaustion persisted for an extended period of time after removing NK cells from the microfluidic platform. Last, the addition of checkpoint inhibitors and immunomodulatory agents alleviated NK cell exhaustion.


Biology ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 70
Author(s):  
Malgorzata Kloc ◽  
Ahmed Uosef ◽  
Martha Villagran ◽  
Robert Zdanowski ◽  
Jacek Z. Kubiak ◽  
...  

The small GTPase RhoA, and its down-stream effector ROCK kinase, and the interacting Rac1 and mTORC2 pathways, are the principal regulators of the actin cytoskeleton and actin-related functions in all eukaryotic cells, including the immune cells. As such, they also regulate the phenotypes and functions of macrophages in the immune response and beyond. Here, we review the results of our and other’s studies on the role of the actin and RhoA pathway in shaping the macrophage functions in general and macrophage immune response during the development of chronic (long term) rejection of allografts in the rodent cardiac transplantation model. We focus on the importance of timing of the macrophage functions in chronic rejection and how the circadian rhythm may affect the anti-chronic rejection therapies.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yanpeng Ding ◽  
Nuomin Liu ◽  
Mengge Chen ◽  
Yulian Xu ◽  
Sha Fang ◽  
...  

Abstract Background BLCA is a common cancer worldwide, and it is both aggressive and fatal. Immunotherapy (ICT) has achieved an excellent curative effect in BLCA; however, only some BLCA patients can benefit from ICT. MT1L is a pseudogene, and a previous study suggested that MT1L can be used as an indicator of prognosis in colorectal cancer. However, the role of MT1L in BLCA has not yet been determined. Methods Data were collected from TCGA, and logistic regression, Kaplan-Meier plotter, and multivariate Cox analysis were performed to demonstrate the correlation between the pseudogene MT1L and the prognosis of BLCA. To identify the association of MT1L with tumor-infiltrating immune cells, TIMER and TISIDB were utilized. Additionally, GSEA was performed to elucidate the potential biological function. Results The expression of MT1L was decreased in BLCA. Additionally, MT1L was positively correlated with immune cells, such as Tregs (ρ = 0.708) and MDSCs (ρ = 0.664). We also confirmed that MT1L is related to typical markers of immune cells, such as PD-1 and CTLA-4. In addition, a high MT1L expression level was associated with the advanced T and N and high grade in BLCA. Increased expression of MT1L was significantly associated with shorter OS times of BLCA patients (p < 0.05). Multivariate Cox analysis revealed that MT1L expression could be an independent prognostic factor in BLCA. Conclusion Collectively, our findings demonstrated that the pseudogene MT1L regulates the immune microenvironment, correlates with poor survival, and is an independent prognostic biomarker in BLCA.


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