NF-κB and Its Regulators During Pregnancy Gómez-Chávez, Fernando; Correa, Dolores; Navarrete-Meneses, Pilar ...
Frontiers in immunology,
05/2021, Letnik:
12
Journal Article
Recenzirano
Odprti dostop
The transcriptional factor NF-κB is a nuclear factor involved in both physiological and pathological processes. This factor can control the transcription of more than 400 genes, including cytokines, ...chemokines, and their modulators, immune and non-immune receptors, proteins involved in antigen presentation and cell adhesion, acute phase and stress response proteins, regulators of apoptosis, growth factors, other transcription factors and their regulators, as well as different enzymes; all these molecules control several biological processes. NF-κB is a tightly regulated molecule that has also been related to apoptosis, cell proliferation, inflammation, and the control of innate and adaptive immune responses during onset of labor, in which it has a crucial role; thus, early activation of this factor may have an adverse effect, by inducing premature termination of pregnancy, with bad outcomes for the mother and the fetus, including product loss. Reviews compiling the different activities of NF-κB have been reported. However, an update regarding NF-κB regulation during pregnancy is lacking. In this work, we aimed to describe the state of the art around NF-κB activity, its regulatory role in pregnancy, and the effect of its dysregulation due to invasion by pathogens like
Trichomonas vaginalis
and
Toxoplasma gondii
as examples.
Recent advances in the field of flow cytometry (FCM) have highlighted the importance of incorporating it as a basic analysis tool in laboratories. FCM not only allows the identification of cell ...subpopulations by detecting the expression of molecules in the cell membrane or cytoplasm, but it can also quantify and identify soluble molecules. The proper functioning of the FCM requires six fundamental systems, from those related to the transport of events to the systems dedicated to the analysis of information. In this review, we have identified the main considerations that every FCM user must know for an optimal antibody panel design, the quality systems that must govern the FCM protocols to guarantee reproducible results in research or clinical laboratories. Finally, we have introduced the current evidence that highlights the relevance of FCM in the investigation and clinical diagnosis of respiratory diseases, establishing important advances in the basic and clinical study of diseases as old as Tuberculosis along with the recent proposals for the monitoring and classification of patients infected with the new SARS-CoV2 virus.
Summary
Most of the work on pomegranate antioxidant and antibacterial activity has been carried out with solvent extracts of different plant or fruit parts. Biosensitive compounds in juice may be ...subject to oxidation, reducing their biological activities. Microencapsulation can be used to protect compounds, allowing its incorporation into functional foods. This study aimed at investigating antioxidant activity after in vitro digestion of microencapsulated juice. Pomegranate juice was encapsulated by spray drying its maltodextrin and gum arabic. The average diameter of the microcapsules was 10–50 µm. We evaluated the bioaccessibility of microencapsulated phenolic compounds by using an in vitro enzymatic digestion. The total phenolic content in digested microencapsulated juice was three times greater than in undigested, indicating that the compounds were made bioaccessible. Digestion also increased antioxidant activity, as measured by ABTS●+ or by DPPH●. Additionally, microencapsulated pomegranate juice showed antibacterial activity against the nine bacteria species tested.
The antimicrobial and antioxidant activity of microencapsulated pomegranate juice after in vitro digestion.
Staphylococcal biofilms significantly contribute to prosthetic joint infection (PJI). However, 40% of S. epidermidis PJI isolates do not produce biofilms, which does not explain the role of biofilms ...in these cases. We studied whether the supernatant from planktonic S. epidermidis alters osteoblast function. Non-biofilm-forming S. epidermidis supernatants (PJI
clinical isolate, healthy skin isolate (HS), and ATCC12228 reference strain) and biofilm-forming supernatants (PJI
clinical isolate, ATCC35984 reference strain, and Staphylococcus aureus USA300 reference strain) were included. Osteoblasts stimulated with supernatants from non-biofilm-forming isolates for 3, 7, and 14 days showed significantly reduced cellular DNA content compared with unstimulated osteoblasts, and apoptosis was induced in these osteoblasts. Similar results were obtained for biofilm-forming isolates, but with a greater reduction in DNA content and higher apoptosis. Alkaline phosphatase activity and mineralization were significantly reduced in osteoblasts treated with supernatants from non-biofilm-forming isolates compared to the control at the same time points. However, the supernatants from biofilm-forming isolates had a greater effect than those from non-biofilm-forming isolates. A significant decrease in the expression of ATF4, RUNX2, ALP, SPARC, and BGLAP, and a significant increase in RANK-L expression were observed in osteoblasts treated with both supernatants. These results demonstrate that the supernatants of the S. epidermidis isolate from the PJI
and HS (commensal) with a non-biofilm-forming phenotype alter the function of osteoblasts (apoptosis induction, failure of cell differentiation, activation of osteoblasts, and induction of bone resorption), similar to biofilm-forming isolates (PJI
, ATCC35984, and S. aureus USA300), suggesting that biofilm status contributes to impaired osteoblast function and that the planktonic state can do so independently of biofilm production.
High-density lipoproteins (HDL) comprise a heterogeneous family of lipoprotein particles divided into subclasses that are determined by density, size and surface charge as well as protein ...composition. Epidemiological studies have suggested an inverse correlation between High-density lipoprotein-cholesterol (HDL-C) levels and the risk of cardiovascular diseases and atherosclerosis. HDLs promote reverse cholesterol transport (RCT) and have several atheroprotective functions such as anti-inflammation, anti-thrombosis, and anti-oxidation. HDLs are considered to be atheroprotective because they are associated in serum with paraoxonases (PONs) which protect HDL from oxidation. Polyphenol consumption reduces the risk of chronic diseases in humans. Polyphenols increase the binding of HDL to PON1, increasing the catalytic activity of PON1. This review summarizes the evidence currently available regarding pharmacological and alternative treatments aimed at improving the functionality of HDL-C. Information on the effectiveness of the treatments has contributed to the understanding of the molecular mechanisms that regulate plasma levels of HDL-C, thereby promoting the development of more effective treatment of cardiovascular diseases. For that purpose, Scopus and Medline databases were searched to identify the publications investigating the impact of current therapies focused on high-density lipoproteins.
Psoriasis is a chronic inflammatory disease distinguished by an excessive proliferation and abnormal differentiation of keratinocytes. Immune cells, such as T lymphocytes and neutrophils, and ...inflammatory cytokines, such as Tumor Necrosis Factor-α (TNF-α) and interleukin 17 (IL-17), are essential for maintaining psoriatic lesions. Additionally, a hypoxic milieu present in the skin promotes the expression of transcriptional factor hypoxia-inducible factor-1 alpha (HIF-1α). This protein regulates the expression of angiogenic and glycolytic factors, such as vascular endothelial grown factor and lactate dehydrogenase (LDH), both relevant in chronic inflammation. The von Hippel-Lindau protein (pVHL) is a negative regulator of HIF-1α. Previously, we found that pVHL was almost absent in the lesions of psoriasis patients; therefore, we investigated the impact of rescue pVHL expression in lesional skin. We used the imiquimod-induced psoriasis-like mouse model as an adenoviral vector that allowed us to express pVHL in the skin. Our data show that, in lesional skin, pVHL expression was reduced, whereas HIF-1α was increased. Remarkably, the retrieval of pVHL prevented psoriatic lesions, diminishing erythema, scale, and epidermal and vascular thickness. Furthermore, pVHL expression was capable of reducing HIF-1α, LDH, TNF-α and immune cell infiltration (mainly IL-17
neutrophils). In conclusion, our results demonstrate that pVHL has a protective role to play in the pathophysiology of psoriasis.
Staphylococci have quorum-sensing (QS) systems that enable cell-to-cell communication, as well as the regulation of numerous colonization and virulence factors. The accessory gene regulator (Agr) ...operon is one of the
Staphylococcus
genus QS systems. Three groups (I, II, and III) are present in
Staphylococcus epidermidis
Agr operon. To date, it is unknown whether Agr groups can interact symbiotically during biofilm development. This study analyzed a symbiotic association among Agr groups during biofilm formation in clinical and commensal isolates. Different combinations among Agr group isolates was used to study biofilm formation
in vitro
and
in vivo
(using a mouse catheter-infection model). The analysis of Agr groups were also performed from samples of human skin (head, armpits, and nostrils). Different predominant coexistence was found within biofilms, suggesting symbiosis type.
In vitro
, Agr I had a competition with Agr II and Agr III. Agr II had a competition with Agr III, and Agr II was an antagonist to Agr I and III when the three strains were combined.
In vivo
, Agr II had a competition to Agr I, but Agr I and II were antagonists to Agr III. The associations found
in vitro
and
in vivo
were also found in different sites of the skin. Besides, other associations were observed: Agr III antagonized Agr I and II, and Agr III competed with Agr I and Agr II. These results suggest that, in
S. epidermidis
, a symbiotic association of competition and antagonism occurs among different Agr groups during biofilm formation.
During pregnancy, NF-κB plays an important role for embryo implantation and the onset of labor. Regulated IL-6 production, under transcriptional control of NF-κB, is essential for a successful ...pregnancy outcome and the atypical regulator IκBNS is involved in this process. Previously, we showed that IκBNS negatively regulates IL-6 in uterine tissues during mouse estrous cycle. In this work, we analyzed if IκBNS and IL-6 expression in pregnant mice under physiological or L. monocytogenes-infected conditions would remain as observed in estrous cycle. In the healthy pregnancy IL-6 was highly expressed during implantation/placentation and labor stages but decreased during fetal development and post-partum stages. In contrast, in mice infected before pregnancy, IL-6 expression was not increased in the implantation stage, and its regulator IκBNS increased more in the infected condition rather than in the healthy pregnancy. IκBNS expression was reduced in post-implantation infection, allowing for IL-6 overexpression. The IκBNS-unrelated cytokine IL-36γ, used as inflammatory cytokine marker, was severely increased in the infected uterine tissues. When we analyzed the effect of infection over the fetuses, we found that pre-implantation infection caused the resorption (rejection) of some products, while the post-implantation infection restricted the intrauterine growth of fetuses. The results suggest that in the uterine tissue of pregnant mice the regulatory effect of IκBNS over IL-6 is more evident in an infection status rather than in a healthy condition.
Biological sciences; Immunology; Health sciences; Women's health; Reproductive system; IL-6, IKBNS, NFKB, Listeria monocytogenes, Pregnancy.
Staphylococcus epidermidis ATCC12228 lipoteichoic acid (LTA) inhibits TNFα production from keratinocytes that are activated with poly I:C. However, this effect has not been proven in clinical or ...commensal isolates.
The <10 kDa fractions of S. epidermidis isolates from ocular infections (n=56), healthy skin (n=35) and healthy conjunctiva (n=32) were obtained. TNFα production was determined by elisa in HaCaT keratinocytes stimulated with poly I:C and with the <10 kDa fractions. LTA in the cytoplasmic membrane and in the <10 kDa fractions of the isolates was determined during bacterial growth by flow cytometry, Western blot and electrospray ionization mass spectrometry. The expression levels of ugtP, ltaA and ltaS were evaluated.
Two populations of isolates were found: a population that inhibited TNFα production (TNFα-inhibitor isolates) and a population that did not inhibit it (TNFα non-inhibitor isolates). The cells from the TNFα-inhibitor isolates had less LTA in the cytoplasmic membrane compared to the cells from the TNFα non-inhibitor isolates (P<0.05). Similarly, LTA was detected in the supernatants of TNFα-inhibitor isolates, and it was absent in TNFα non-inhibitor isolates. High expression levels of the ugtP and ltaA genes in the 1850I (TNFα-inhibitor isolate) and 37HS (TNFα non-inhibitor isolate) isolates were found during bacterial growth. However, the ltaS gene had a low expression level (P<0.05) in the 37HS isolate.
The TNFα-inhibitor isolates release LTA due to high expression of the LTA synthesis genes. By contrast, TNFα non-inhibitor isolates do not release LTA due to low expression level of the ltaS gene.
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