AI Article Synopsis

  • - The study investigated how lipopolysaccharide (LPS) and heat shock induction affect heat shock protein-90α (HSP90α) and cytokine levels in peripheral blood mononuclear cells (PBMCs) from patients with septic shock, trauma-related SIRS, and healthy individuals, using specific experimental conditions.
  • - Results showed that heat shock significantly increased HSP90α levels across all groups, with distinct responses in cytokine production, especially heightened in trauma cases, while glutamine treatment had mixed effects on HSP90α modulation in sepsis and SIRS.
  • - Overall, glutamine at 10 mM modified HSP90α expression in unpredictable ways depending on timing relative to LPS

Article Abstract

We aimed to assess the lipopolysaccharide (LPS), or heat shock (HS) induction, and glutamine-modulating effects on heat shock protein-90α (HSP90α) and cytokines in an ex vivo model using peripheral blood mononuclear cells (PBMCs). The PBMCs of patients with septic shock, trauma-related systemic inflammatory response syndrome (SIRS), and healthy subjects were incubated with 1 μg/mL LPS at 43 °C (HS). Glutamine 10 mM was added 1 hour before or after induction or not at all. We measured mRNA HSP90α, monocyte (m) and lymphocyte (l) HSP90α proteins, interleukin (IL)-1b, -6, -8, -10, tumor necrosis factor-α (TNF-α), and monocyte chemoattractant protein-1 (MCP-1) supernatant levels. Heat shock increased the HSP90α mRNA and mHSP90α in all groups (10-fold in sepsis, p < 0.001 and p = 0.047, respectively). LPS induced the mHSP90α and lHSP90α in healthy (p < 0.001) and mHSP90α in SIRS (p = 0.004) but not in sepsis. LPS induced the cytokines at 24 and 48 h in all groups, especially in trauma (p < 0.001); HS only induced the IL-8 in healthy (p = 0.003) and septic subjects (p = 0.05). Glutamine at 10 mM before or after stimulation did not alter any induction effect of LPS or HS on HSP90α mRNA and mHSP90α protein in sepsis. In SIRS, glutamine before LPS decreased the mHSP90α but increased it when given after HS (p = 0.018). Before or after LPS (p = 0.049) and before HS (p = 0.018), glutamine decreased the lHSP90α expression in sepsis but increased it in SIRS when given after HS (p = 0.003). Regarding cytokines, glutamine enhanced the LPS-induced MCP-1 at 48 h in healthy (p = 0.011), SIRS (p < 0.001), and sepsis (p = 0.006). In conclusion, glutamine at 10 mM, before or after LPS and HS, modulates mHSP90α and lHSP90α in sepsis and SIRS differently and unpredictably. Although it does not alter the stimulation effect on interleukins, glutamine enhances the LPS induction effect on supernatant MCP-1 in all groups. Future research should seek to elucidate better the impact of glutamine and temperature modulation on HSP90α and MCP-1 pathways in sepsis and trauma.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9824313PMC
http://dx.doi.org/10.3390/nu15010252DOI Listing

Publication Analysis

Top Keywords

heat shock
12
glutamine
9
lps
9
sepsis
8
sepsis trauma
8
peripheral blood
8
blood mononuclear
8
mononuclear cells
8
hsp90α mrna
8
mrna mhsp90α
8

Similar Publications

Drought is a persistent and serious threat to crop yield and quality. The identification and functional characterization of drought tolerance-related genes is thus vital for efforts to support the genetic improvement of drought-tolerant crops. Barley is highly adaptable and renowned for its robust stress resistance, making it an ideal subject for efforts to explore genes related to drought tolerance.

View Article and Find Full Text PDF

Age-related differences in gene expression and pathway activation following heat stroke.

Physiol Genomics

December 2024

Experimental Medicine Department, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs, Riyadh, 11481, Saudi Arabia.

This study investigates the molecular responses to heat stroke in young and old patients by comparing whole-genome transcriptomes between age groups. We analyzed transcriptomic profiles from patients categorized into two age-defined cohorts: young (mean age = 44.9 ± 6 years) and old (mean age = 66.

View Article and Find Full Text PDF

Targeting angiogenic and proliferative mediators by montelukast & trimetazidine Ameliorates thioacetamide-induced liver fibrosis in rats.

Toxicol Appl Pharmacol

December 2024

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, 35516 Mansoura, Egypt; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura National University, Gamasa, 7731168, Egypt.

Liver fibrosis is a significant health complication with the potential to result in serious mortality and morbidity. However, there is no standard treatment due to its complex pathogenesis. The drug montelukast reversibly and selectively antagonizes the cysteinyl-leukotrienes-1 receptor and reduces inflammation; thus, it is used in the treatment of asthma.

View Article and Find Full Text PDF

Chronic inflammatory diseases, e.g., obesity, cardiovascular disease, and type 2 diabetes, progressively suppress the anti-inflammatory heat shock response (HSR) by impairing the synthesis of key components, perpetuating inflammation.

View Article and Find Full Text PDF

Fibrosis, characterised by excessive extracellular matrix deposition, contributes to both organ failure and significant mortality worldwide. Whereas fibroblasts are activated into myofibroblasts, marked by phenotypic factors such as α-smooth muscle actin (α-SMA), periostin, fibroblast activation protein (FAP) and heat shock protein 47 (HSP47), the cellular processes of trans-differentiation for fibrosis development remain poorly understood. Herein, we hypothesised that the molecular signalling of geranylgeranyl pyrophosphate (GGPP), a crucial biochemical molecule for protein prenylation, is essential in the regulation of profibrotic mechanisms for fibroblast-to-myofibroblast activation.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!

A PHP Error was encountered

Severity: Notice

Message: fwrite(): Write of 34 bytes failed with errno=28 No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 272

Backtrace:

A PHP Error was encountered

Severity: Warning

Message: session_write_close(): Failed to write session data using user defined save handler. (session.save_path: /var/lib/php/sessions)

Filename: Unknown

Line Number: 0

Backtrace: