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Differential Effect of Extracellular Acidic Environment on IL-1? Released from Human and Mouse Phagocytes.

ABSTRACT: Areas of locally decreased pH are characteristic for many chronic inflammatory diseases such as atherosclerosis and rheumatoid arthritis, acute pathologies such as ischemia reperfusion, and tumor microenvironment. The data on the effects of extracellular acidic pH on inflammation are conflicting with respect to interleukin 1 beta (IL-1?) as one of the most potent proinflammatory cytokines. In this study, we used various mouse- and human-derived cells in order to identify potential species-specific differences in IL-1? secretion pattern in response to extracellular acidification. We found that a short incubation in mild acidic medium caused significant IL-1? release from human macrophages, however, the same effect was not observed in mouse macrophages. Rather, a marked IL-1? suppression was observed when mouse cells were stimulated with a combination of various inflammasome instigators and low pH. Upon activation of cells under acidic conditions, the cytosolic pH was reduced while metabolic activity and the expression of the main inflammasome proteins were not affected by low pH. We show that IL-1? secretion in mouse macrophages is reversible upon restoration of physiological pH. pH sensitivity of NLRP3, NLRC4 and AIM2 inflammasomes appeared to be conferred by the processes upstream of the apoptosis-associated speck-like protein containing a CARD (ASC) oligomerization and most likely contributed by the cell background rather than species-specific amino acid sequences of the sensor proteins.

SUBMITTER: Susjan P

PROVIDER: S-EPMC7582253 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Differential Effect of Extracellular Acidic Environment on IL-1β Released from Human and Mouse Phagocytes.

Sušjan Petra P Benčina Mojca M Hafner-Bratkovič Iva I

International journal of molecular sciences 20200930 19

Areas of locally decreased pH are characteristic for many chronic inflammatory diseases such as atherosclerosis and rheumatoid arthritis, acute pathologies such as ischemia reperfusion, and tumor microenvironment. The data on the effects of extracellular acidic pH on inflammation are conflicting with respect to interleukin 1 beta (IL-1β) as one of the most potent proinflammatory cytokines. In this study, we used various mouse- and human-derived cells in order to identify potential species-specif ...[more]

PMID: 33007998

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Differential Effect of Extracellular Acidic Environment on IL-1? Released from Human and Mouse Phagocytes.

Publications

Differential Effect of Extracellular Acidic Environment on IL-1β Released from Human and Mouse Phagocytes.

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