著者

古賀 農人 戸田 裕之 木下 学 吉野 相英

出版者

一般社団法人 日本エンドトキシン・自然免疫研究会

雑誌

エンドトキシン・自然免疫研究 (ISSN:24341177)

巻号頁・発行日

vol.22, pp.30-34, 2019 (Released:2019-11-06)

参考文献数

4

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Most of the current depression drugs have been developed based on the monoamine hypothesis. However, about 30% of patients indicate resistance to medication, and patients with relatively mild depression get only a small benefit from antidepressants. In addition, although an increase in monoamine concentration in synaptic gaps by monoamine transporter inhibition occurs within a relatively short time, it takes about six weeks to show an antidepressant effect in actual clinical settings. There are cases in which an antidepressant effect is observed for drugs that do not regulate the amount of monoamine. These facts suggest the presence of a variety of pathophysiologies in depression and depressive symptoms. Recently, a relationship between the onset of depression and the expression levels of immune-related molecules such as cytokines in the blood and the brain derived from patients with depression has been pointed out. Although there is so far no medication targeting neuroinflammation, many recent studies have shown that inflammation is not negligible and a significant factor in the pathogenesis of depression. Therefore, it is meaningful to focus on inflammation for elucidating the pathogenesis and developing medications. In this paper, we describe the pathogenesis pathways known to be involved in the inflammation, the serotonin hypothesis, hypothalamic-pituitary-adrenal axis hypothesis, and neurodegeneration/neurogenesis hypothesis and describe the applications to therapy and preventions based on them.

著者

齋藤 伸一郎

出版者

一般社団法人 日本エンドトキシン・自然免疫研究会

雑誌

エンドトキシン・自然免疫研究 (ISSN:24341177)

巻号頁・発行日

vol.21, pp.1-6, 2018 (Released:2018-11-22)

参考文献数

22

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Toll-like receptor (TLR) recognizes viral and bacterial specific components to activate immune responses. TLR plays an essential role for a pathogen sensor. TLR can be divided two groups by their localization. One is cell surface TLR which localizes in cell membrane to recognize mainly bacterial cell wall components. The other is nucleic acid-sensing TLRs, which localize in endosome or lysosome in immune cells to recognize viral and bacterial nucleic acids. We have investigated about TLR trafficking to regulate TLR7 activation. First, I want to introduce TLR4 trafficking and activation mechanism as a cell surface receptor which recognizes gram-negative bacterial cell wall component LPS. Second, I want to introduce TLR7 trafficking and activation mechanism as an endo-lysosomal TLR to recognize bacterial and viral RNAs.

著者

山崎 達也 千葉 丈 高村 (赤司) 祥子

出版者

一般社団法人 日本エンドトキシン・自然免疫研究会

雑誌

エンドトキシン・自然免疫研究 (ISSN:24341177)

巻号頁・発行日

vol.21, pp.7-11, 2018 (Released:2018-11-22)

参考文献数

12

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Classical passive immunization has provided the benefit to prevent against infectious diseases for over century. Although lots of antibody-drugs have been developed for cancer and autoimmune disease, those against infectious disease are rarely available. Because it has complex reasons including the current availability of antimicrobial drugs, small markets, high costs, and microbial antigenic variation. We firstly demonstrated long-prophylaxis against influenza virus (A/Puerto Rico/8/34, IAV) using plasmids encoding neutralizing IgG monoclonal antibodies. Antibody gene-based injection could induce stable and high expression level of the neutralizing antibodies, which was possible that single inoculation protected the mice against a lethal dose of IAV infection. We proposed that this method could dissolve problems of high cost to the purification, limited supply for pandemic, and the risk of using viral vectors. We also succeeded to treatment against IAV infection using antibody gene-based injection by hydrodynamics (HD), which was involving rapid inoculation of a large volume of plasmid-DNA solution into mice via the tail vein. HD could rapidly induce the potent level of neutralizing antibodies in the serum within 24 hours. We demonstrated that a single HD completely protected the mice even after a lethal dose of IAV infection. Finally, we also generated other isotypes of antibody-gene to exchange from IgG to IgA, IgM, IgD, and IgE to retain the variable region. The neutralizing IgA was most effective at reducing upper respiratory tract IAV infection. Thus, our passive immunotherapy could provide a new prophylaxis/therapeutic strategy of targeting IAV infection.

著者

髙村 (赤司) 祥子

出版者

一般社団法人 日本エンドトキシン・自然免疫研究会

雑誌

エンドトキシン・自然免疫研究 (ISSN:24341177)

巻号頁・発行日

vol.22, pp.79-82, 2019 (Released:2019-11-06)

参考文献数

6

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The bee venom (BV) is the secretion which is produced by a needle device for protection the bee from an enemy. However, BV has been applied to the folk medicine for various diseases because it is included many enzymes which are containing anti-inflammatory or anti-cancer action. Above all, Phospholipase A2 (PLA2) is a hydrolytic enzyme which cleaves membrane phospholipids, and in bee venom occupying up to 12%. PLA2 has been analyzed in greatest detail. This mini review sets out the latest scientific evidence concerning the therapeutic effects of PLA2 in the context of diseases and provides a detailed description of the mechanisms.

著者

四釜 洋介 黒澤 実愛 松下 健二

出版者

一般社団法人 日本エンドトキシン・自然免疫研究会

雑誌

エンドトキシン・自然免疫研究 (ISSN:24341177)

巻号頁・発行日

vol.22, pp.40-42, 2019 (Released:2019-11-06)

参考文献数

9

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Interleukin (IL) -29 is a cytokine belonging to the type Ⅲ interferon family, which regulates a similar set of genes as type Ⅰ interferons. Although type Ⅰ interferons act globally, type Ⅲ interferons primarily target epithelial cells and protect them against the frequent viral attacks that are common for barrier tissues. The antiviral effects of IL-29 have been demonstrated at barrier surfaces in the respiratory and gastrointestinal tracts, liver, blood-brain barrier, and skin, but it remains unknown whether IL-29 exhibits these effects in oral epithelial cells. In this study, we found that the functional IL-29 receptor, interferon-lambda receptor 1, is expressed in epithelial cells from both human oral mucosa and gingiva, but not in human gingival fibroblasts. Although IL-29 stimulation did not induce pro-inflammatory cytokine mRNA expression, such as IL-6 and IL-8, it did induce retinoic acid-inducible gene (RIG) -I and interferon gamma-inducible protein 16 (IFI-16) production via a signal transducers and activator of transcription 1 (STAT1) -dependent pathway in gingival epithelial cells. RIG-I and IFI-16 sense viral nucleic acids, and the stimulation of these receptors induces interferon beta production. Moreover, we confirmed that the augmenting effects of IL-29 on 5’triphosphate double-stranded RNA (a synthetic ligand for RIG-I) -induced interferon beta production in gingival epithelial cells. These data suggest the therapeutic potential of IL-29 for preventing viral infections in the oral mucosa.

著者

土谷 正和

出版者

一般社団法人 日本エンドトキシン・自然免疫研究会

雑誌

エンドトキシン・自然免疫研究 (ISSN:24341177)

巻号頁・発行日

vol.23, pp.43-46, 2020 (Released:2020-10-29)

参考文献数

13

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Limulus amebocyte lysate (LAL) is widely used for detection of endotoxin, one of the most potent pyrogen. Recent studies revealed the mechanism of activation of Factor C and Factor B, endotoxin binding proteins in LAL cascade. It is well known that Factor C is the first factor to bind endotoxin aggregates. The second coagulation factor, Factor B is important to achieve specificity of LAL to endotoxin because activated Factor C on endotoxin aggregates are essential for its activation. The endotoxin-specific signal is amplified after the Factor B activation in LAL. On the other hand, recombinant Factor C reagents rely on only the specificity of Factor C to endotoxin, and amplifies the trypsin-like activity of activated Factor C that may not be specific to endotoxin. This mechanism seems not to be as specific to endotoxin as LAL. More evaluation and improvement are necessary for recombinant reagents for endotoxin measurement as a safety test.

著者

高橋 徹

出版者

一般社団法人 日本エンドトキシン・自然免疫研究会

雑誌

エンドトキシン・自然免疫研究 (ISSN:24341177)

巻号頁・発行日

vol.21, pp.62-65, 2018 (Released:2018-11-22)

参考文献数

6

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HSR incites pulmonary inflammation that leads to acute respiratory distress syndrome (ARDS). However, there have been no definitive pharmacological therapies against ARDS. CO is a toxic gas due to the generation of carboxyhemoglobin (COHb). However, trace amount of CO is endogenously produced by the enzymatic reaction of heme oxygenase-1 (HO-1) that is induced by oxidative stress to confer protection against various inflammatory disorders. Recent studies have indicated that low dose of CO exerts potent cytoprotective effects on inflammatory organ damage in animal models by its anti-inflammatory property. We also demonstrated that CO inhalation at 250 ppm ameliorated HSR-induced pulmonary injury in rats. However, this dose of CO increased blood COHb level to approximately 20% that may be toxic to humans. Very recently, to overcome the disadvantage, CORMs have been developed by coordinating CO with a transition metal carbonyl complexes. Among various types of CORMs, CORM-3, a water-soluble CORM, spontaneously liberated and deliver CO to various tissues under physiological condition through intravenous administration. We found that CORM-3 treatment mitigated HSR-induced lung injury without any increase in blood COHb levels through its anti-inflammatory property. We propose that CO/CORMs are possible pharmacological agent to treat ARDS.

著者

清水 智治 三宅 亨 北村 直美 遠藤 善裕 谷 徹 谷 眞至

出版者

一般社団法人 日本エンドトキシン・自然免疫研究会

雑誌

エンドトキシン・自然免疫研究 (ISSN:24341177)

巻号頁・発行日

vol.23, pp.1-6, 2020 (Released:2020-10-29)

参考文献数

4

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Toraymyxin® (Toray Medical Co., Ltd, Tokyo, Japan) has been developed as a direct hemoperfusion column that contains polymyxin B-immobilized fiber to bind endotoxins in the patients’ blood. Toraymyxin was approved by the Japanese National Health Insurance system for the treatment of endotoxemia and septic shock in 1994. We reviewed and analyzed clinical history and evidence of Toraymyxin, and assessed the current status of Toraymyxin use for the treatment of severe sepsis and septic shock. Our review shows that Toraymyxin appeared to be effective in improving hemodynamics and respiratory function in septic shock requiring emergency abdominal surgery. The recent large-scale RCTs could not demonstrate whether prognosis is improved by Toraymyxin. The clinical studies based on large-scale data-base from Japan revealed that Toraymyxin appeared to have a survival benefit in patients with severe condition of septic shock. We also commented on the revised version of health insurance adaptation of Toraymyxin in April, 2020.

著者

土谷 正和

出版者

一般社団法人 日本エンドトキシン・自然免疫研究会

雑誌

エンドトキシン・自然免疫研究 (ISSN:24341177)

巻号頁・発行日

vol.21, pp.23-25, 2018 (Released:2018-11-22)

参考文献数

7

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Low Endotoxin Recovery (LER) is a phenomenon of endotoxin activity decrease in a matrix containing a chelating agent and a detergent, and is a controversial topic in the biopharmaceutical field. The mechanism of LER is not fully elucidated. When endotoxin in LER solutions was diluted with water, the activity was decreased. The activity was maintained for a long time at 4°C, and was recovered by magnesium dilution and direct addition to the Limulus amebocyte lysate (LAL). The size of endotoxin in LER solution was not changed after the activity was decreased. Considering these results, a new LER mechanism was proposed. A chelating agent removes divalent cations from the surface of endotoxin aggregates, and endotoxin molecules on the surface of the aggregates are replaced with detergent molecules. The reduction of the surface area of endotoxin aggregates causes decrease of the endotoxin activity to the LAL.