Differential Effect of Extracellular Acidic Environment on IL-1β Released from Human and Mouse Phagocytes
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 wit...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/19/7229 |
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| author | Petra Sušjan Mojca Benčina Iva Hafner-Bratkovič |
| author_facet | Petra Sušjan Mojca Benčina Iva Hafner-Bratkovič |
| author_sort | Petra Sušjan |
| collection | DOAJ |
| description | 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-specific differences in IL-1β secretion pattern in response to extracellular acidification. We found that a short incubation in mild acidic medium caused significant IL-1β release from human macrophages, however, the same effect was not observed in mouse macrophages. Rather, a marked IL-1β 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-1β 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. |
| first_indexed | 2024-03-10T15:56:27Z |
| format | Article |
| id | doaj.art-fd5280906a4f4c08b2dc5e2662438312 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T15:56:27Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-fd5280906a4f4c08b2dc5e26624383122023-11-20T15:40:20ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-09-012119722910.3390/ijms21197229Differential Effect of Extracellular Acidic Environment on IL-1β Released from Human and Mouse PhagocytesPetra Sušjan0Mojca Benčina1Iva Hafner-Bratkovič2Department of Synthetic Biology and Immunology, National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana, SloveniaDepartment of Synthetic Biology and Immunology, National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana, SloveniaDepartment of Synthetic Biology and Immunology, National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana, SloveniaAreas 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-specific differences in IL-1β secretion pattern in response to extracellular acidification. We found that a short incubation in mild acidic medium caused significant IL-1β release from human macrophages, however, the same effect was not observed in mouse macrophages. Rather, a marked IL-1β 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-1β 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.https://www.mdpi.com/1422-0067/21/19/7229acidosisIL-1βinflammasomespecies-specificNLRP3 |
| spellingShingle | Petra Sušjan Mojca Benčina Iva Hafner-Bratkovič Differential Effect of Extracellular Acidic Environment on IL-1β Released from Human and Mouse Phagocytes International Journal of Molecular Sciences acidosis IL-1β inflammasome species-specific NLRP3 |
| title | Differential Effect of Extracellular Acidic Environment on IL-1β Released from Human and Mouse Phagocytes |
| title_full | Differential Effect of Extracellular Acidic Environment on IL-1β Released from Human and Mouse Phagocytes |
| title_fullStr | Differential Effect of Extracellular Acidic Environment on IL-1β Released from Human and Mouse Phagocytes |
| title_full_unstemmed | Differential Effect of Extracellular Acidic Environment on IL-1β Released from Human and Mouse Phagocytes |
| title_short | Differential Effect of Extracellular Acidic Environment on IL-1β Released from Human and Mouse Phagocytes |
| title_sort | differential effect of extracellular acidic environment on il 1β released from human and mouse phagocytes |
| topic | acidosis IL-1β inflammasome species-specific NLRP3 |
| url | https://www.mdpi.com/1422-0067/21/19/7229 |
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