Hemorrhagic Shock Activation of NLRP3 Inflammasome in Lung Endothelial Cells
Open accessAbstract
Hemorrhagic shock (HS) due to major trauma and surgery predisposes the host to the development of systemic inflammatory response syndrome (SIRS), including acute lung injury (ALI), through activating and exaggerating the innate immune response. IL-1β is a crucial proinflammatory cytokine that contributes to the development of SIRS and ALI. Lung endothelial cells (EC) are one important source of IL-1β, and the production of active IL-1β is controlled by the inflammasome. In this study, we addressed the mechanism underlying HS activation of the inflammasome in lung EC. We show that high mobility group box 1 acting through TLR4, and a synergistic collaboration with TLR2 and receptor for advanced glycation end products signaling, mediates HS-induced activation of EC NAD(P)H oxidase. In turn, reactive oxygen species derived from NAD(P)H oxidase promote the association of thioredoxin-interacting protein with the nucleotide-binding oligomerization domain-like receptor protein NLRP3 and subsequently induce inflammasome activation and IL-1β secretion from the EC. We also show that neutrophil-derived reactive oxygen species play a role in enhancing EC NAD(P)H oxidase activation and therefore an amplified inflammasome activation in response to HS. The present study explores a novel mechanism underlying HS activation of EC inflammasome and thus presents a potential therapeutic target for SIRS and ALI induced after HS.
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HMGB1 has been found to prime the NLRP3 inflammasome.
“HMGB1 has been found to prime the NLRP3 inflammasome (Xiang et al, 2011).”
From Danger Signals and Inflammasomes: Stress-Evoked Sterile Inflammation in Mood Disorders (2017) · cites this paper as Xiang et al, 2011
HMGB-1 increased NLRP3 mRNA and protein and acts as a priming stimulus for the NLRP3 inflammasome.
“Indeed, HMGB-1 increased NLRP3 mRNA and protein (Xiang et al, 2011;Frank et al, 2015a) and acts as a priming stimulus for the NLRP3 inflammasome (Frank et al, 2015a).”
From Repeated Social Defeat, Neuroinflammation, and Behavior: Monocytes Carry the Signal (2017) · cites this paper as Xiang et al, 2011
RSD-induced monocytes are recruited to the CNS to promote anxiety-like behavior.
“Clear evidence that RSD-induced monocytes are recruited to the CNS to promote anxiety-like behavior.”
From Repeated Social Defeat, Neuroinflammation, and Behavior: Monocytes Carry the Signal (2017) · cites this paper as [143]
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- Authors
- Xiang, M., Shi, X., Li, Y., Xu, J., Yin, L., Xiao, G., Scott, M. J., Billiar, T. R., Wilson, M. A., & Fan, J.
- Affiliations
- Shanghai Medical College of Fudan University (CN)
- Department of Surgery, University of Pittsburgh School of Medicine , Pittsburgh, PA 15213
- University of Pittsburgh (US)
- Corresponding author
- Li, Yuehua
- Xu, Jia
- Fan, Jie
- ORCID
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-11-01
- Volume
- 187
- Issue
- 9
- Pages
- 4809-4817
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- PMC
- PMC3197874
- OpenAlex
- W2111548114
- Cited by
- 155
- References
- 61
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 8 · 2023: 4 · 2022: 13 · 2021: 9 · 2020: 10 · 2019: 12 · 2018: 19 · 2017: 9 · 2016: 17 · 2015: 12 · 2014: 15 · 2013: 15 · 2012: 6
- FWCI
- 4.65
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL079669)
- National Institute of General Medical Sciences (P50GM053789, R01GM102146)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK072230)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR059647)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Keywords
- hemorrhagic shock, NLRP3 inflammasome, pulmonary endothelial cells, IL-1β secretion, high mobility group box 1, TLR4, TLR2, receptor for advanced glycation end products, NADPH oxidase, reactive oxygen species, TXNIP, neutrophils, acute lung injury, systemic inflammatory response syndrome, innate immunity
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Animals, Carrier Proteins, Cells, Cultured, Disease Models, Animal, Endothelium, Vascular, Lung, Male, Mice, Inbred C57BL, Mice, Transgenic, Shock, Hemorrhagic, Mice, Knockout, Respiratory Mucosa, HMGB1 Protein, Mice, Interleukin-1beta, Inflammasomes
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