Cannabinoid Receptor Ligands Modulate Fibrosis and Inflammation in Idiopathic Pulmonary Fibrosis: a Preliminary Study

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2024

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Tubitak Scientific & Technological Research Council Turkey

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Nutrition and Dietetics
(2017)
Student admission to the Atılım University Department of Nutrition and Dietetics started in 2017. Our Department is the only academic institution to offer undergraduate-level education completely in English in the field of Nutrition and Dietetics in Ankara. The studies of our department may be classified into two main categories; education and research. The current education programs are offered taking into consideration the awareness of the responsibility in offering a degree in Nutrition and Dietetics; by competent instructors in the field, and with an inter-disciplinary approach. Our aim for the future alumni of our undergraduate program is to undertake their responsibilities in the light of their information with a professional insight, and the confidence to constantly update themselves at hospitals, polyclinics, public health centers, ministries, catering institutions, food companies, universities and such where they may be employed in positions such as health care professionals, academicians, researchers, directors or policy makers.

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Background/aim: No specific pharmacological treatment regimen for idiopathic pulmonary fibrosis (IPF) exists. Therefore, new antiinflammatory therapeutic strategies are needed. Cannabinoids (CBs), known for their inflammation-modulating and antifibrotic effects, may be potential medication candidates for treating IPF. We aim to evaluate the inflammation-modulating and antifibrotic effects of CB receptor (CBR) agonists and antagonists in lipopolysaccharide-stimulated normal human lung fibroblast, epithelial cells, IPF fibroblast cells, and monocytes. Materials and methods: We detected CBRs in normal human lung fibroblasts (LL24) and IPF fibroblast cells (LL29), epithelial cells (A549) and monocytes (THP-1) by flow cytometry. We determined TGF-(31, IL-8, and TNF-alpha inflammatory cytokines in the LL24, LL29, A549, and THP-1 cell culture supernatants on days 1 and 5 by ELISA. We evaluated the cell viability in LL24, LL29, and A549 cells on days 1, 3, and 5 spectrophotometrically and detected collagen Type I (ColI) production in the LL24 and LL29 cell culture supernatants on days 1, 3, and 5 by ELISA. Results: LL24, LL29, A549, and THP-1 cells exhibited CB1 (CB1R) and CB2 (CB2R) receptors. CB1R and CB2R agonists WIN55,2122 and JWH015 inhibited fibroblastic and epithelial cell proliferation on day 5. TGF-(31 and TNF-alpha release increased, while IL-8 release decreased in LL24, LL29, A549, and THP-1 cells in response to the administration of WIN55,212-2 and JWH015 at a 10-2 mM concentration. CB1R and CB2R antagonists AM251 and AM630 did not block agonistic responses, suggesting a nonclassical CBRmediated pathway. CB2R agonist JWH015 decreased ColI expression in IPF lung fibroblasts LL29 on day 3. Conclusion: These results suggest that CB signaling regulates the progression of pulmonary inflammation and fibrosis via CBR activation. This may offer a potential pharmacological tool for developing antifibrosis therapies.

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Idiopathic pulmonary fibrosis, cannabinoid, cannabinoid receptor, inflammation, fibrosis

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48

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6

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https://doi.org/10.55730/1300-0152.2713
 https://hdl.handle.net/20.500.14411/10414

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