Pneumologie 2024; 78(S 01): S65-S66
DOI: 10.1055/s-0044-1778878
Abstracts
COPD, Bronchiektasie, Cystische Fibrose

Activation of the IGF-1 pathway by Trofinetide as a novel therapeutic approach for asthma and COPD

Authors

  • X Nguyen

    1   Department of Pneumology, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany.

  • E Papakonstantinou

    2   Department of Pneumology, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany.; Clinic of Respiratory Medicine and Pulmonary Cell Research, University Hospital, 4031 Basel, Switzerland.

  • C Ntenti

    3   Faculty of Medicine, University of Freiburg; Department of Pneumology

  • M Christopoulou

    4   Biochemistry, Biochemical Analysis & Matrix Pathobiology Res. Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, Patras, Greece; Freiburg University Medical Center, University Clinic Freiburg, Clinic for Pneumology; Department of Pneumology, Medical Center – University of Freiburg, Faculty of Medicine

  • D Stolz

    5   Universitätsklinikum Freiburg; Klinik für Pneumologie, Department Innere Medizin, Medizinische Fakultät, Albert Ludwigs Universität, Freiburg, Deutschland; Clinic of Respiratory Medicine and Pulmonary Cell Research
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Introduction: Asthma and COPD are common diseases characterised by chronic inflammation, airway remodelling and hyperreactivity. Conventional treatments such as bronchodilators and corticosteroids have their limitations due to side effects and efficacy issues. Insulin-like growth factor 1 (IGF-1) is a multifunctional peptide involved in inflammation, cell proliferation, and differentiation. Trofinetide, a synthetic analog peptide of IGF-1, shows promise in modulating neuroinflammatory signalling pathways and cellular responses and opens new therapeutic opportunities for these respiratory diseases. The aim of this study was to investigate the interaction of trofinetide with the IGF-1 signalling pathway, and its anti-inflammatory effects in human bronchial epithelial cells.

Methods Human bronchial epithelial cells were pre-treated with TNF-α for 1 hour before the addition of trofinetide or vehicle for various time points. Gene and protein levels of IL-1β, IL-6 and IL-8 were determined by ELISA and by quantitative PCR.

Results Stimulation of human bronchial epithelial cells with TNF-α enhanced gene and protein expression of proinflammatory cytokines, including IL -1β, IL -6, and IL -8. Trofinetide administration attenuated the TNF-α-mediated inflammatory responses. Trofinetide treatment significantly decreased TNF-α-induced gene expression of IL -1β, IL -6 and IL -8 after 1 hour. The strongest attenuation was observed after 6 hours incubation with trofinetide at a concentration of 100 µM, resulting in a 40% decrease in IL -6 and a 45% decrease in IL -8 secretion.

Conclusions Trofinetide inhibits the TNF-α-induced cytokine expression in human bronchial epithelial cells, reducing their inflammatory response. Our findings shed light on novel therapies for inflammation-related diseases such as asthma and COPD.



Publication History

Article published online:
01 March 2024

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