炎症の代謝はAMPKと偽飢餓によって制限される

Luke A J O'Neill¹, D Grahame Hardie

¹School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland. laoneill@tcd.ie

Nature

|January 18, 2013

まとめ

細胞代謝は炎症に大きく影響する. 炎症を誘発する細胞は糖分解の増加を示し,抗炎症細胞は酸化代謝に依存し,免疫反応における代謝の再プログラムを示唆する.

科学分野:

免疫メタボリズムは
炎症における細胞代謝

背景:

活性化マクロファージやTヘルパー17細胞などの炎症性細胞は,代謝の変化を示します.
これらの代謝変化には,グルコースの吸収,グリコリシス,およびペントースリン酸経路の活性性の増加が含まれます.
低酸素誘導因子1αとAMP活性化タンパク質キナーゼは,これらの炎症性代謝変化における対極的な役割が提案されています.

研究の目的:

プロ炎症性および抗炎症性両方の免疫細胞における代謝の再プログラムを探求する.
免疫細胞の機能と炎症を調節する代謝経路の役割を理解する.

主な方法:

異なる免疫細胞タイプ (例えば,M1対M2マクロファージ,Th17対Treg細胞) の代謝プロファイルの比較分析.
低酸素誘導因子1αおよびAMP活性化タンパク質キナーゼなどの主要な代謝調節体の調査.
糖分解,酸化リン酸化,ペントースリン酸経路を含む代謝経路の評価.

主要な成果:

炎症を誘発する細胞は,糖分解とペントースリン酸経路の活性が強化されていることを示している.
抗炎症細胞は,低血糖分解率と高酸化代謝を示す.
抗炎症剤によるAMP活性化タンパク質キナーゼの活性化により,偽飢餓状態が誘発される可能性があります.

結論:

代謝の変化は,プロ炎症性および抗炎症性両方の免疫細胞の機能に不可欠です.
細胞代謝をターゲットにすることは,炎症を調節するための潜在的な治療戦略です.

さらに関連する動画

09:41

Measuring the Rate of Lipolysis in Ex Vivo Murine Adipose Tissue and Primary Preadipocytes Differentiated In Vitro

Published on: March 17, 2023

08:01

Measurement of Insulin- and Contraction-Stimulated Glucose Uptake in Isolated and Incubated Mature Skeletal Muscle from Mice

Published on: May 16, 2021

関連する概念動画

01:24

Metabolic States of the Body: Fasting and Starvation

During the initial hours of fasting, the body uses up its glycogen stores as an energy source. Once these glycogen reserves are depleted, the body begins breaking down stored triglycerides and structural proteins. During this stage, glycerol becomes a key substrate for gluconeogenesis, while free fatty acids undergo beta-oxidation to provide energy for tissues, such as skeletal muscle. In the fasting state, the body spares protein breakdown as much as possible to conserve muscle and structural...

01:18

Metabolic States of the Body: The Postabsorptive State

The postabsorptive state usually starts about four hours after a meal and lasts until the next meal is eaten. During this time, the digestive system stops absorbing nutrients, and the body uses stored energy reserves to maintain stable blood glucose levels.
Initially, glycogen stored in the liver is broken down to release glucose into the bloodstream, while glycogen in the muscles is broken down to supply glucose for energy directly within the muscle cells. As glycogen stores diminish,...

01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a rapamycin-insensitive companion...

01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...

01:12

Chronic Inflammation: Introduction

Chronic inflammation is a prolonged, dysregulated immune response that persists for weeks to years when the inciting stimulus is difficult to eradicate or when self‑antigens drive ongoing reactivity. Morphologically, it is defined by mononuclear cell infiltration, progressive tissue destruction, and concurrent attempts at healing via angiogenesis and fibrosis. Compared with acute inflammation, edema is less prominent while cellular infiltration predominates; triggers include persistent...

01:38

Inflammation

Overview

関連する実験動画