Intracerebroventricular (icv) injection of transient receptor potential vanilloid 4 (TRPV4) agonists 4α-phorbol-12, 13-didecanoate (4α-PDD) and GSK101690A increased urinary excretion under the ...physiological condition. TRPV4 antagonists ruthenium red and HC-067047 significantly blocked increased urinary volume after intragastric administration of water and 4α-PDD-induced diuresis. Administration of the TRPV4 agonists did not significantly change the plasma concentration of vasopressin or atrial natriuretic factor. Pretreatment with indomethacin inhibited the diuresis induced by 4α-PDD. Moreover, icv injection of prostaglandin (PG) F2α produced diuretic effects. These findings indicate that central TRPV4 regulates urine excretion, which contributes to systemic water homeostasis in vivo. The underlying mechanisms are suggested to involve PG synthesis, but not release of vasopressin or atrial natriuretic factor.
The decidua has been known as maternal uterine tissue, which plays essential roles in protecting the embryo from being attacked by maternal immune cells and provides nutritional support for the ...developing embryo prior to placenta formation. However, there are questions that still remain to be answered: (1) How does the decidua supply nutrition and provide a physical scaffold for the growing embryo, before placental vascular connection is established? (2) How is the balance between preventing an anti-embryo immune response and protecting both embryo and mother from infections established? To understand basic personas in decidual tissues, we review the structure of the decidua composed of terminally differentiated uterine stromal cells, blood vessels, and a number of repertoire of uterine local immune cells, including the well-known uterine natural killer (uNK) cells and recently discovered innate lymphoid cells (ILCs). Decidual macrophages and uterine dendritic cells (DCs) are supposed to modulate adaptive immunity via balancing cytokines and promoting generation of regulatory T (T
reg
) cells. During decidualization, vascular and tissue remodeling in the uterus provide nutritional and physical support for the developing embryo. Secretion of various cytokines and chemokines from both the embryo and the decidual cells activates multiple signaling network between the mother and the embryo upon implantation. Defects in the decidual development during early pregnancy result in loss of pregnancy or complications in later gestational stage.
This essay introduces the stories of four former residents of a municipal housing complex built in the late 1950s in central Tokyo. In the immediate aftermath of World War II, the interviewees and ...their families had found shelter in and around an abandoned Imperial Japanese Army base. After moving them into concrete housing blocks in order to hide their settlement prior to Tokyo's hosting of the Olympics in 1964, the city moved them again in preparation for the 2020 Olympics. Their stories reveal the ways that war and defeat left the city’s population to fend for themselves, as well as the long tug‐of‐war that ensued between the interests of settlers and those of the municipal and national governments.
Acute kidney injury (AKI) is associated with prolonged hospitalization and high mortality, and it predisposes individuals to chronic kidney disease. To date, no effective AKI treatments have been ...established. Here we show that the apoptosis inhibitor of macrophage (AIM) protein on intraluminal debris interacts with kidney injury molecule (KIM)-1 and promotes recovery from AKI. During AKI, the concentration of AIM increases in the urine, and AIM accumulates on necrotic cell debris within the kidney proximal tubules. The AIM present in this cellular debris binds to KIM-1, which is expressed on injured tubular epithelial cells, and enhances the phagocytic removal of the debris by the epithelial cells, thus contributing to kidney tissue repair. When subjected to ischemia-reperfusion (IR)-induced AKI, AIM-deficient mice exhibited abrogated debris clearance and persistent renal inflammation, resulting in higher mortality than wild-type (WT) mice due to progressive renal dysfunction. Treatment of mice with IR-induced AKI using recombinant AIM resulted in the removal of the debris, thereby ameliorating renal pathology. We observed this effect in both AIM-deficient and WT mice, but not in KIM-1-deficient mice. Our findings provide a basis for the development of potentially novel therapies for AKI.
There are many different pathogenic stimuli that are able to activate the immune system, ranging from microbes that include bacteria, viruses, fungi, and parasites to host-derived triggers such as ...autoantigens that can induce autoimmunity as well as neoantigens involved in tumorigenesis. One of the key interactions shaping immunity toward these triggers involves the encounter of antigen-processing and -presenting cells such as macrophages and dendritic cells with T cells, resulting in immune responses that are highly selective for the antigenic trigger. Research over the past few years has implicated members of the coronin protein family, in particular coronin 1, in responses against several pathogenic triggers. While coronin 1 was initially described as a host factor allowing the intracellular survival of the pathogen
, subsequent work showed it to be a crucial factor for naïve T cell homeostasis. The activity of coronin 1 in allowing the intracellular survival of pathogenic mycobacteria is relatively well characterized, involving the activation of the Ca
/calcineurin pathway, while coronin 1's role in modulating naïve T cell homeostasis remains more enigmatic. In this mini review, we discuss the knowledge on the role for coronin 1 in immune cell functioning and provide a number of potential scenarios
which coronin 1 may be able to regulate naïve T cell homeostasis.
Following thymic maturation, T cells egress as recent thymic emigrants to peripheral lymphoid organs where they undergo an additional maturation step to mature naive T cells that circulate through ...secondary lymphoid organs ready to be activated upon pathogenic challenges. Thymic maturation and peripheral T cell survival depend on several signaling cascades, but whether a dedicated mechanism exists that exclusively regulates homeostasis of mature naive T cells without affecting thymocytes and/or recent thymic emigrants remains unknown. In this article, we provide evidence for a specific and exclusive role of the WD repeat containing protein coronin 1 in the maintenance of naive T cells in peripheral lymphoid organs. We show that coronin 1 is dispensable for thymocyte survival and development, egress from the thymus, and survival of recent thymic emigrants. Importantly, coronin 1-deficient mice possessed comparable levels of peripheral T cells within the first 2 wk after birth but failed to populate the peripheral T cell compartment at later stages. Furthermore, dendritic cell- and IL-2/7-dependent T cell survival was found to be independent of coronin 1. Together, these results suggest the existence of a hitherto unrecognized coronin 1-dependent decision switch early during life that is responsible for peripheral naive T cell survival and homeostasis.
Aji-narezushi (salted and fermented horse mackerel with rice) and
kaburazushi (salted and fermented turnip with yellowtail and malted rice) are traditional lactic acid-fermented foods in Japan. In ...this study, we screened lactose utilizable, acidophilic and antioxidative lactic acid bacteria (LAB) from
aji-narezushi and
kaburazushi for use as a starter of various fermented foods, as well as for probiotics. Of the 177 LAB isolated strains, 57 strains fermented lactose and among these, 28 grew in MRS broth adjusted to pH 4.5. All of these 28 strains were lactobacilli and produced lactic acid in 50% Japanese white radish (
daikon) juice at 15
°C. The fermented
daikon juice increased the superoxide radical (
O
2
-
) scavenging capacity, but did not change clearly the DPPH
− scavenging capacity and ferrous reducing power. The
O
2
-
scavenging activity component was fractionated to <5
kDa by ultrafiltration. Three selected strains (two from
aji-narezushi and three from
kaburazushi) that showed high scavenging activity are identified to
Lactobacillus plantarum by 16S rRNA sequence identity and carbohydrate utilization test (API-CHL50). These
L. plantarum strains could ferment milk at 42
°C, like yogurt starters, and the
O
2
-
scavenging activity was increased by fermentation. These results suggest that the
L. plantarum strains can be used as profitable starter organisms and probiotics.
Microbes have interacted with eukaryotic cells for as long as they have been co-existing. While many of these interactions are beneficial for both the microbe as well as the eukaryotic cell, several ...microbes have evolved into pathogenic species. For some of these pathogens, host cell invasion results in irreparable damage and thus host cell destruction, whereas others use the host to avoid immune detection and elimination. One of the latter pathogens is
, arguably one of the most notorious pathogens on earth. In mammalian macrophages,
manages to survive within infected macrophages by avoiding intracellular degradation in lysosomes using a number of different strategies. One of these is based on the recruitment and phagosomal retention of the host protein coronin 1, that is a member of the coronin protein family and a mammalian homolog of coronin A, a protein identified in
. Besides mediating mycobacterial survival in macrophages, coronin 1 is also an important regulator of naïve T cell homeostasis. How, exactly, coronin 1 mediates its activity in immune cells remains unclear. While in lower eukaryotes coronins are involved in cytoskeletal regulation, the functions of the seven coronin members in mammals are less clear.
coronins may have maintained multiple functions, whereas the mammalian coronins may have evolved from regulators of the cytoskeleton to modulators of signal transduction. In this minireview, we will discuss the different studies that have contributed to understand the molecular and cellular functions of coronin proteins in mammals and
.
Hepatocellular carcinoma (HCC) is a widespread fatal disease and the third most common cause of cancer deaths. Here, we show the potent anti-HCC effect of the circulating protein AIM. As in ...adipocytes, AIM is incorporated into normal hepatocytes, where it interferes with lipid storage. In contrast, AIM accumulates on the HCC cell surface and activates the complement cascade via inactivating multiple regulators of complement activation. This response provokes necrotic cell death specifically in AIM-bound HCC cells. Accordingly, AIM(-/-) mice were highly susceptible to steatosis-associated HCC development, whereas no AIM(+/+) mouse developed the disease despite comparable liver inflammation and fibrosis in response to a long-term high-fat diet. Administration of AIM prevented tumor development in AIM(-/-) mice, and HCC induction by diethylnitrosamine was more prominent in AIM(-/-) than wild-type mice. These findings could be the basis for novel AIM-based therapeutic strategies for HCC.
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