Shizuo Akira

Bio: Shizuo Akira is an academic researcher from Osaka University. The author has contributed to research in topics: Innate immune system & Immune system. The author has an hindex of 261, co-authored 1308 publications receiving 320561 citations. Previous affiliations of Shizuo Akira include University of California, Berkeley & Wakayama Medical University.

Regulation of mRNA stability by CCCH-type zinc-finger proteins in immune cells.

Abstract: Current studies using knockout mice have revealed that some Cys-Cys-Cys-His (CCCH)-type zinc-finger proteins, namely tristetraprolin (TTP), Roquin and Regnase-1, play important roles in the immune system. These proteins are closely associated with the fate of their target RNAs in normal immune responses. However, the functions of many RNA-binding proteins have not been characterized precisely. To understand the molecular mechanisms of RNA metabolism in the immune system, investigation of TTP/Roquin/Regnase-1 might provide new knowledge. In this review, we will discuss the current understanding of these proteins in immune regulation and homeostasis and discuss RNA metabolism in the immune system.

Interferon response induced by Toll-like receptor signaling.

Abstract: Toll-like receptors (TLRs) are essential for the recognition of distinct pathogen-associated molecular patterns (PAMPs). Activation of TLRs induces intracellular signaling pathways which lead to the production of pro-inflammatory cytokines, chemokines, and interferon (IFN)-inducible genes. TIR domain containing adaptor molecules in turn determine the signaling specificity of the response. Recent studies demonstrated that serine/threonine kinases IKK-i/TBK1 are critical for the regulation of IFN-beta as well as IFN-inducible genes. In response to lipopolysaccharide (LPS), transfection of poly(I:C) and viral infection, embryonic fibroblasts (MEFs) derived from TBK1-deficient (TBK1-/-) mice show impaired production of IFN-inducible genes, but not proinflammatory cytokines. Although IKK-i-/- mice show normal production of these genes, MEFs from IKK-i/TBK1-doubly deficient mice were completely defective in the induction of IFN-beta as well as IFN-inducible genes in response to poly(I:C) stimulation. Activation of IFN-regulatory factor (IRF) 3 in response to LPS and poly(I:C) was abolished in IKK-i/TBK1 doubly deficient cells. Interestingly, intracellular transduction of poly(I:C) initiates activation of IFN response in a TLR3-independent manner. These observations demonstrate that IKK-i/TBK1 signaling is essential for both TLR3-dependent and TLR3-independent viral and dsRNA-induced IFN responses.

Microsomal prostaglandin E synthase‐1 is induced in alzheimer's disease and its deletion mitigates alzheimer's disease‐like pathology in a mouse model

Abstract: Epidemiological studies have suggested that long-term use of nonsteroidal anti-inflammatory drugs that inhibit cyclooxygenase (COX) activity can moderate the onset or progression of Alzheimer's disease (AD). Thus it has been suggested that prostaglandin E2 (PGE2), a major end-product of COX, may play a pathogenic role in AD, but the involvement of PGE synthase (PGES), a terminal enzyme downstream from COX, has not been fully elucidated. Here we found that, among three PGES enzymes, only microsomal PGES-1 (mPGES-1) is induced, and its expression is associated with β-amyloid (Aβ) plaques in the cerebral cortex in human AD patients and in Tg2576 mice, a transgenic AD mouse model. Furthermore, to investigate whether mPGES-1 contributes to AD-like pathology, we bred mPGES-1-deficient mice with Tg2576 mice. We found that mPGES-1 deletion reduced the accumulation of microglia around senile plaques and attenuated learning impairments in Tg2576 mice. These results indicated that mPGES-1 is induced in the AD brain and thus plays a role in AD pathology. Blockage of mPGES-1 could form the basis for a novel therapeutic strategy for patients with AD. Inc. © 2013 Wiley Periodicals, Inc.

Functional V region formation during in vitro culture of a murine immature B precursor cell line

Abstract: B lymphocytes originate from pluripotential haematopoietic stem cells and differentiate into immunoglobulin (Ig)-producing cells. B-cell lineage differentiation is accompanied by two types of immunoglobulin gene rearrangements--rearrangement of V, D and J gene segments to create a functional V gene and rearrangement of CH genes for heavy-chain switching. These results, however, have been obtained mainly by analysis of immunoglobulin gene organization of myeloma cells. Baltimore and his colleagues have established Abelson murine leukaemia virus (A-MuLV)-transformed cell lines and found a few lines capable of carrying out kappa-gene rearrangement or undergoing isotype switching during in vitro culture. To study early B-cell lineage differentiation events, we have now also established A-MuLV-transformed cell lines which are capable of differentiating from mu- to mu+ and of undergoing continuing rearrangement of heavy-chain genes in culture. Analysis of immunoglobulin gene organization of these transformed cells revealed that mu- cells have already undergone DNA rearrangements involving JH segments but an additional rearrangement of JH segments is required for initiation of mu-chain synthesis. Southern blot analysis of the DNA and two-dimensional gel electrophoresis of intracytoplasmic mu-chain show that mu-chain diversity with respect to antigen specificity may be generated during this second rearrangement process. As no rearrangement of light-chain genes takes place in these cells, this implies that light-chain gene rearrangement requires some further change, or a different enzyme.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine.

Abstract: Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a world...

Cancer-related inflammation.

Abstract: The mediators and cellular effectors of inflammation are important constituents of the local environment of tumours. In some types of cancer, inflammatory conditions are present before a malignant change occurs. Conversely, in other types of cancer, an oncogenic change induces an inflammatory microenvironment that promotes the development of tumours. Regardless of its origin, 'smouldering' inflammation in the tumour microenvironment has many tumour-promoting effects. It aids in the proliferation and survival of malignant cells, promotes angiogenesis and metastasis, subverts adaptive immune responses, and alters responses to hormones and chemotherapeutic agents. The molecular pathways of this cancer-related inflammation are now being unravelled, resulting in the identification of new target molecules that could lead to improved diagnosis and treatment.