The DOI matches its Crossref record; 66 of the 66 references it cites were found in a registry or an index.
Extracellular Acidosis Is a Novel Danger Signal Alerting Innate Immunity via the NLRP3 Inflammasome
Open accessAbstract
BACKGROUND: Local acidosis has been demonstrated in ischemic tissues and at inflammatory sites. RESULTS: Acidic extracellular pH triggers NLRP3 inflammasome activation and interleukin-1β secretion in human macrophages. CONCLUSION: Acidic pH represents a novel danger signal alerting the innate immunity. SIGNIFICANCE: Local acidosis may promote inflammation at ischemic and inflammatory sites. Local extracellular acidification has been demonstrated at sites of ischemia and inflammation. IL-1β is one of the key proinflammatory cytokines, and thus, its synthesis and secretion are tightly regulated. The NLRP3 (nucleotide-binding domain leucine-rich repeat containing family, pyrin domain containing 3) inflammasome complex, assembled in response to microbial components or endogenous danger signals, triggers caspase-1-mediated maturation and secretion of IL-1β. In this study, we explored whether acidic environment is sensed by immune cells as an inflammasome-activating danger signal. Human macrophages were exposed to custom cell culture media at pH 7.5-6.0. Acidic medium triggered pH-dependent secretion of IL-1β and activation of caspase-1 via a mechanism involving potassium efflux from the cells. Acidic extracellular pH caused rapid intracellular acidification, and the IL-1β-inducing effect of acidic medium could be mimicked by acidifying the cytosol with bafilomycin A1, a proton pump inhibitor. Knocking down the mRNA expression of NLRP3 receptor abolished IL-1β secretion at acidic pH. Remarkably, alkaline extracellular pH strongly inhibited the IL-1β response to several known NLRP3 activators, demonstrating bipartite regulatory potential of pH on the activity of this inflammasome. The data suggest that acidic environment represents a novel endogenous danger signal alerting the innate immunity. Low pH may thus contribute to inflammation in acidosis-associated pathologies such as atherosclerosis and post-ischemic inflammatory responses.
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Pattern recognition receptors and central nervous system repair
Kigerl, K. A., de Rivero Vaccari, J. P., Dietrich, W. D., Popovich, P. G., & Keane, R. W. (2014) · Experimental Neurology · doi:10.1016/j.expneurol.2014.01.001 · Cited by 490
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Mechanical stiffness controls dendritic cell metabolism and function
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Metadata
- Authors
- Rajamäki, K., Nordström, T., Nurmi, K., Åkerman, K. E. O., Kovanen, P. T., Öörni, K., & Eklund, K. K.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2013-05
- Volume
- 288
- Issue
- 19
- Pages
- 13410-13419
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2123251003
- Cited by
- 355
- References
- 66
- FWCI
- 10.22
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Rajamäki, K., Nordström, T., Nurmi, K., Åkerman, K. E. O., Kovanen, P. T., Öörni, K., & Eklund, K. K. (2013). Extracellular Acidosis Is a Novel Danger Signal Alerting Innate Immunity via the NLRP3 Inflammasome. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m112.426254
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