Interplay of Heat Shock Proteins and Oxidative Stress in Modulating Neutrophil Activation in Cystic Fibrosis Inflammation
Background: Cystic fibrosis, is an autosomal recessive disorder characterized by persistent inflammation, unregulated immune responses, and pneumonic complications. The central role of CF-associated inflammation is neutrophil activation triggered by oxidative stress and Heat Shock Proteins (HSPs)....
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
ziauddin University
2025-04-01
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| Series: | Pakistan Journal of Medicine and Dentistry |
| Subjects: | |
| Online Access: | https://ojs.zu.edu.pk/pjmd/article/view/3295 |
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| Summary: | Background: Cystic fibrosis, is an autosomal recessive disorder characterized by persistent inflammation, unregulated immune responses, and pneumonic complications. The central role of CF-associated inflammation is neutrophil activation triggered by oxidative stress and Heat Shock Proteins (HSPs). The present study seeks to explore the interaction of oxidative stress, HSPs, and neutrophil activation in CF patients.
Methods: A case-control study was conducted from January-2023 to June-2024 at the School of Pain Regenerative Medicine, The University of Lahore, including 100 CF patients and 100 age and gender-matched controls. A purposive sampling method was employed to recruit participants for this retrospective case-control study. Serum MDA, 4-HNE, 8-OHdG, and isoprostanes were quantified. The HSP27, HSP70, and HSP90, neutrophil activation was measured using neutrophil elastase, myeloperoxidase, and matrix metalloproteinase-9. Values are expressed as mean±SD with a significance threshold of p < 0.05.
Results: The MDA values were (5.89±1.38 nmol/mg), 4-HNE (18.3±4.63 mol/L). HSP27 levels were significantly increased (72.53±12.27 ng/mL), HSP70 (110.23±15.67 ng/mL), and HSP90 (88.6±14.21 ng/mL). Neutrophil activation markers, (250.88±35.16 g/L) and MPO (340.01 42.22 ng/mL) were significantly increased. Neutrophil elastase (200 g/L) has a high sensitivity (83%) (95 % CI: 4.36-14.25), which is a significant predictor of neutrophil-driven inflammation.
Conclusion: The findings suggest that neutrophil activation and sustained inflammation in CF are caused by HSPs and oxidative stress. Elevated HSPs and oxidative stress markers are associated with increased pneumonic inflammation. Novel curative measures to reduce CF-associated inflammation are likely to be developed through target HSPs and oxidative stress variables.
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| ISSN: | 2313-7371 2308-2593 |