Zhou et al. (Nature) and Hoffmann et al. (Cell) identify ACE2 as a SARS-CoV-2 receptor, and the latter show its entry mechanism depends on cellular serine protease TMPRSS2. These results may explain ...proinflammatory cytokine release via the associated angiotestin II pathway and a possible therapeutic target via the IL-6-STAT3 axis.
Understanding the cell entry mechanism of pandemic coronavirus SARS-CoV-2 is crucial for treating the disease. Zhou et al. (Nature) and Hoffmann et al. (Cell) identify ACE2 as a SARS-CoV-2 receptor, and the latter show its entry mechanism depends on cellular serine protease TMPRSS2. These results suggest several possible therapeutic targets, including the IL-6-STAT3 axis previously associated with cytokine release syndromes.
We shall study minimal complex surfaces with
c
2
=
9
and
χ
=
5
whose canonical classes are divisible by 3 in the integral cohomology groups, where
c
1
2
and
χ
denote the first Chern number of an ...algebraic surface and the Euler characteristic of the structure sheaf, respectively. The main results are a structure theorem for such surfaces, the unirationality of the moduli space, and a description of the behavior of the canonical map. As a byproduct, we shall also rule out a certain case mentioned in a paper by Ciliberto–Francia–Mendes Lopes. Since the irregularity
q
vanishes for our surfaces, our surfaces have geometric genus
p
g
=
4
.
Since the molecular cloning of interleukin-6 (IL-6) in 1986, many other cytokines have been found to share the same signal transducer, gp130, in their receptor complexes. Thus, the IL-6 family of ...cytokines now consists of ten members. Although some of the family members’ functions are redundant as a result of the expression of gp130, there are also functional distinctions between members. The mechanisms that determine functional redundancies and distinctions are not completely understood. Yet, research has clarified the role of IL-6 family cytokines in autoimmune diseases and has led to effective therapies that target them. Here, we review the IL-6 family of cytokines in autoimmune diseases, with a particular focus on the prototypical member IL-6, from the viewpoints of their structure, signaling, and biological features and discuss possible mechanisms of their functional pleiotropy.
Ten receptors for cytokines in the IL-6 family share the signal transducer gp130. Some functions of these cytokines are redundant, but others are distinct and specific. Murakami et al. review the IL-6 cytokine family from the viewpoints of structure, signaling, and biological features and discuss mechanisms of their functional pleiotropy.
Zinc (Zn) is an essential heavy metal that is incorporated into a number of human Zn metalloproteins. Zn plays important roles in nucleic acid metabolism, cell replication, and tissue repair and ...growth. Zn deficiency is associated with a range of pathological conditions, including impaired immunity, retarded growth, brain development disorders and delayed wound healing. Moreover, many reports have suggested that Zn is involved in cancer development and levels of Zn in serum and malignant tissues of patients with various types of cancer are abnormal. Zn may directly affect tumor cells by regulating gene expression profiles and/or cell viability, both of which are mediated in part by tumor‐induced changes in Zn transporter expression. On the other hand, Zn may indirectly influence tumor cells by affecting processes within the cancer microenvironment, including immune responses; the functions and/or activity levels of immune cells that attack tumor cells are influenced by the intracellular Zn concentrations within those cells. In both cases, Zn contributes to intracellular metal homeostasis and/or signal transduction in tumor and immune cells. In this review article, we will summarize the current understanding of the roles of Zn homeostasis and signaling primarily in immune cells, with a discussion of the contributions of these processes to oncogenesis. (Cancer Sci 2008; 99: 1515–1522)
The newly emerging coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China, but has rapidly spread all over the ...world. Some COVID-19 patients encounter a severe symptom of acute respiratory distress syndrome (ARDS) with high mortality. This high severity is dependent on a cytokine storm, most likely induced by the interleukin-6 (IL-6) amplifier, which is hyper-activation machinery that regulates the nuclear factor kappa B (NF-κB) pathway and stimulated by the simultaneous activation of IL-6-signal transducer and activator of transcription 3 (STAT3) and NF-κB signaling in non-immune cells including alveolar epithelial cells and endothelial cells. We hypothesize that IL-6-STAT3 signaling is a promising therapeutic target for the cytokine storm in COVID-19, because IL-6 is a major STAT3 stimulator, particularly during inflammation. We herein review the pathogenic mechanism and potential therapeutic targets of ARDS in COVID-19 patients.
Abstract
We have been studying inflammatory diseases, with a special focus on IL-6, and discovered two concepts related to inflammation development. One is the gateway reflex, which is induced by the ...activation of specific neural circuits followed by establishing gateways for autoreactive CD4+ T cells to pass through blood barriers toward the central nervous system (CNS) and retina during tissue-specific inflammatory diseases. We found that the formation of these gateways is dependent on the IL-6 amplifier, which is machinery for enhanced NF-κB activation in endothelial cells at specific sites. We have found five gateway reflexes in total. Here, we introduce the gateway reflex and the IL-6 amplifier.
Abstract
The immune and nervous systems share many features, including receptor and ligand expression, enabling efficient communication between the two. Accumulating evidence suggests that the ...communication is bidirectional, with the neural system regulating immune cell functions and vice versa. Steroid hormones from the hypothalamus–pituitary–adrenal gland axis are examples of systemic regulators for this communication. Neural reflexes describe regional regulation mechanisms that are a historically new concept that helps to explain how the neural and body systems including immune system communicate. Several recently identified neural reflexes, including the inflammatory reflex and gateway reflex, significantly impact the activation status of the immune system and are associated with inflammatory diseases and disorders. Either pro-inflammatory or anti-inflammatory effects can be elicited by these neural reflexes. On the other hand, the activities of immune cells during inflammation, for example the secretion of inflammatory mediators, can affect the functions of neuronal systems via neural reflexes and modulate biological outputs via specific neural pathways. In this review article, we discuss recent advances in the understanding of bidirectional neuro-immune interactions, with a particular focus on neural reflexes.
Abstract
We have reported the gateway reflex, which describes specific neural activations that regulate immune cell gateways at specific blood vessels in the central nervous system (CNS). Four types ...of gateway reflexes exist, all of which induce alterations in endothelial cells at specific vessels of the blood-brain barrier followed by inflammation in the CNS in the presence of CNS-autoreactive T cells. Here we report a new gateway reflex that suppresses the development of retinal inflammation by using an autoreactive T cell-mediated ocular inflammation model. Exposure to photopic light down-regulated the adrenoceptor pathway to attenuate ocular inflammation by suppressing breaching of the blood-retina barrier. Mechanistic analysis showed that exposure to photopic light down-regulates the expression of α
1A
-adrenoceptor (α
1A
AR) due to high levels of norepinephrine and epinephrine, subsequently suppressing inflammation. Surgical ablation of the superior cervical ganglion (SCG) did not negate the protective effect of photopic light, suggesting the involvement of retinal noradrenergic neurons rather than sympathetic neurons from the SCG. Blockade of α
1A
AR signaling under mesopic light recapitulated the protective effect of photopic light. Thus, targeting regional adrenoceptor signaling might represent a novel therapeutic strategy for autoimmune diseases including those that affect organs separated by barriers such as the CNS and eyes.
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