Inflammatory response plays an essential role in the resolution of infections. However, inflammation can be detrimental to an organism and cause irreparable damage. For example, during sepsis, a cytokine storm can lead to multiple organ failures and often results in death. One of the strongest triggers of the inflammatory response is bacterial lipopolysaccharides (LPS), acting mostly through Toll-like receptor 4 (TLR4). Paradoxically, while exposure to LPS triggers a robust inflammatory response, repeated or prolonged exposure to LPS can induce a state of endotoxin tolerance, a phenomenon where macrophages and monocytes do not respond to new endotoxin challenges, and it is often associated with secondary infections and negative outcomes. The cellular mechanisms regulating this phenomenon remain elusive. We used metabolic measurements to confirm differences in the cellular metabolism of naïve macrophages and that of macrophages responding to LPS stimulation or those in the LPS-tolerant state. In parallel, we performed an unbiased secretome survey using quantitative mass spectrometry during the induction of LPS tolerance, creating the first comprehensive secretome profile of endotoxin-tolerant cells. The secretome changes confirmed that LPS-tolerant macrophages have significantly decreased cellular metabolism and that the proteins secreted by LPS-tolerant macrophages have a strong association with cell survival, protein metabolism, and the metabolism of reactive oxygen species.
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http://dx.doi.org/10.3390/biom11020164 | DOI Listing |
Front Biosci (Schol Ed)
December 2024
Laboratory of Genomic Research, Research Institute for Genetic and Molecular Epidemiology, Kursk State Medical University, 305041 Kursk, Russia.
Background: Disruptions in proteostasis are recognized as key drivers in cerebro- and cardiovascular disease progression. Heat shock proteins (HSPs), essential for maintaining protein stability and cellular homeostasis, are pivotal in neuroperotection. Consequently, deepening the understanding the role of HSPs in ischemic stroke (IS) risk is crucial for identifying novel therapeutic targets and advancing neuroprotective strategies.
View Article and Find Full Text PDFFront Biosci (Elite Ed)
October 2024
Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, 1983969411 Tehran, Iran.
Background: Regenerative endodontics requires an innovative delivery system to release antibiotics/growth factors in a sequential trend. This study focuses on developing/characterizing a thermoresponsive core-shell hydrogel designed for targeted drug delivery in endodontics.
Methods: The core-shell chitosan-alginate microparticles were prepared by electrospraying to deliver bone morphogenic protein-2 for 14 days and transforming growth factor-beta 1 (TGF-β1) for 7-14 days.
Front Biosci (Landmark Ed)
December 2024
Mackenzie Cancer Research Group, Department of Pathology and Biomedical Science, University of Otago Christchurch, 8011 Christchurch, Aotearoa New Zealand.
Tumor-associated macrophages (TAMs) are innate immune cells that exert far reaching influence over the tumor microenvironment (TME). Depending on cues within the local environment, TAMs may promote tumor angiogenesis, cancer cell invasion and immunosuppression, or, alternatively, inhibit tumor progression via neoantigen presentation, tumoricidal reactive oxygen species generation and pro-inflammatory cytokine secretion. Therefore, TAMs have a pivotal role in determining tumor progression and response to therapy.
View Article and Find Full Text PDFJ Integr Neurosci
December 2024
Cerebral Palsy Center in Neurosurgery, Second Affiliated Hospital of Xinjiang Medical University, 830063 Urumqi, Xinjiang, China.
Cerebral palsy (CP), a common neurological disorder in children, remains a significant research focus. The interleukin (IL) family, pivotal mediators in inflammatory responses, shows increased expression in various neuroinflammatory diseases, markedly influencing their onset and progression. Elevated IL levels in the brains of children with CP, in contrast to healthy peers, reflect similar elevations in neurological conditions linked to CP, indicating a strong association between CP and the IL family.
View Article and Find Full Text PDFJ Inflamm Res
December 2024
Department of Internal and Emergency Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
Purpose: Septic cardiomyopathy (SCM) is a significant global public health concern characterized by substantial morbidity and mortality, which has not been improved for decades due to lack of early diagnosis and effective therapies. This study aimed to identify hub biomarkers in SCM and explore their potential mechanisms.
Methods: We utilized the GSE53007 and GSE207363 datasets for transcriptome analysis of normal and SCM mice.
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