Inhibition of Janus Kinase 2 and Signal Transduction and Activator of Transcription 3 Protect Against Cecal Ligation and Puncture-Induced Multiple Organ Damage and Mortality
Abstract
Background Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway plays an important role in sepsis, transducing a multitude of inflammatory signals. To date, knowledge of JAK/STAT pathway in sepsis is limited. This study was to investigate the potential role of JAK/STAT pathway in mediating multiple organ damage and mortality in septic rats. Our data showed that inhibition of JAK2/STAT3 attenuated cecal ligation and puncture-induced multiple organ damage and mortality in 48 hours in rats. Methods A total of 98 male Wistar rats were randomly divided into 4 groups as follows: (1) normal control group (n = 10); (2) cecal ligation and puncture (CLP) group (n = 40), which was further divided into 2, 6, 24, 48-hour post-CLP groups; (3) AG490 (8.0 mg/kg, Calbiochem, La Jolla, CA) treatment group (n = 24), which was further divided into 2, 6, 24, 48-hour post-CLP groups; (4) rapamycin (0.4 mg/kg, Calbiochem, Calbiochem, La Jolla, CA) treatment group (n = 24), which was further divided into 2, 6, 24, 48-hour post-CLP groups; CLP was performed to induce experimental sepsis. AG490 (8 mg/kg) or rapamycin (0.4 mg/kg) was injected subcutaneously 0.5 hour before CLP in respective group. Animals were killed at destined time after CLP (not including the death rate observation group), and specimens of serum, liver, and lungs were harvested and stored in liquid nitrogen for subsequent analyses. In an additional experiment, 88 animals were randomly divided into three…
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AG490 treatment protected against liver and lung injury and improved survival in CLP-induced sepsis and LPS-induced toxic shock in mice.
“AG490 treatment protected against liver and lung injury and improved survival in CLP‐induced sepsis and LPS‐induced toxic shock in mice. 29 , 30 , 31”
From Sepsis induces interleukin 6, gp130/JAK2/STAT3, and muscle wasting (2022) · cites this paper as [31]
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Darnell, J. E., Kerr, L. M., & Stark, G. R. (1994) · Science · doi:10.1126/science.8197455 · Cited by 6,080 · cited 2× · see citing works
“For example, interferon (IFN)- employs the JAK/STAT pathway for its signal transduction to augment the innate immune response initiated by LPS, TNF- , or IL-1, and proinflammatory effect of IL-6 is mainly mediated by STAT1/3.4,5 Thus, blockade of JAK/STAT pathway at the right time as well as in the appropriate point p…”
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The role of JAK/STAT signaling pathway and its inhibitors in diseases.
Xin, P., Xu, X., Deng, C., Liu, S., Wang, Y., Zhou, X., Ma, H., Wei, D., & Sun, S. (2020) · International Immunopharmacology · doi:10.1016/j.intimp.2020.106210 · Cited by 1,010 · see citing works
Kang, R., Chen, R., Zhang, Q., Hou, W., Wu, S., Cao, L., Huang, J., Yu, Y., Fan, X.-G., Yan, Z., et al. (2014) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2014.05.001 · Cited by 956 · see citing works
Self-citationSepsis induces interleukin 6, gp130/JAK2/STAT3, and muscle wasting
Zanders, L., Kny, M., Hahn, A., Schmidt, S., Wundersitz, S., Todiras, M., Lahmann, I., Bandyopadhyay, A., Wollersheim, T., Kaderali, L., et al. (2022) · Journal of Cachexia, Sarcopenia and Muscle · doi:10.1002/jcsm.12867 · Cited by 225 · see citing works
- Authors
- Hui, L., Yao, Y., Wang, S., Yu, Y., Dong, N., Li, H., & Sheng, Z.
- Affiliations
- Chinese PLA General Hospital (CN)
- Venue
- Journal of Trauma: Injury, Infection & Critical Care
- Published
- 2009-03
- Volume
- 66
- Issue
- 3
- Pages
- 859-865
- ISSN
- 0022-5282 (ISSN-L)
- OpenAlex
- W2050236162
- Cited by
- 42
- References
- 1
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 3 · 2022: 5 · 2021: 4 · 2020: 3 · 2018: 1 · 2017: 5 · 2016: 2 · 2015: 3 · 2014: 3 · 2013: 2 · 2012: 4
- FWCI
- 1.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Trauma: Injury, Infection, and Critical Care (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
- Keywords
- JAK/STAT signaling, JAK2 inhibition, STAT3 inhibition, sepsis, cecal ligation and puncture, multiple organ injury, mortality, AG490, rapamycin, myeloperoxidase, neutrophil infiltration, liver injury, lung injury, inflammatory cytokines, IL-1β, interleukin-6, TNF-α, IL-10
- MeSH terms
- Alanine Transaminase, Animals, Aspartate Aminotransferases, Cecum, Drug Administration Schedule, Enzyme Inhibitors, Male, Multiple Organ Failure, Peroxidase, Signal Transduction, Survival Rate, Rats, Wistar, Tyrphostins, Sirolimus, HMGB1 Protein, STAT3 Transcription Factor, Rats, Janus Kinase 2
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