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Turkish Journal of Biology

Abstract

Background/aim: There is no specific pharmacological treatment regimen for idiopathic pulmonary fibrosis (IPF). Therefore, new anti-inflammatory therapeutic strategies are needed. Cannabinoids (CBs) that are known for their inflammation-modulating and anti-fibrotic effects may be potential medication candidates for the treatment of IPF. Our aim is to evaluate the inflammation-modulating and anti-fibrotic effects of CB receptor (CBR) agonists and antagonists in lipopolysaccharide (LPS) stimulated human lung healthy fibroblast, epithelial cells, IPF fibroblast cells and monocytes.Materials and methods: We detected CBRs in the human lung healthy (LL24) and IPF fibroblast cells (LL29), epithelial cells (A549) and monocytes (THP-1) by flow cytometry (FC). We determined TGF-β1, IL-8 and TNF-α inflammatory cytokines in the LL24, LL29, A549 and THP-1 cell culture supernatants on day 1 and 5 by ELISA. We evaluated the cell viability in LL24, LL29 and A549 cells on days 1, 3 and 5 spectrophotometrically. We 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 presented CB1 (CB1R) and CB2 (CB2R) receptors. CB1R and CB2R agonists WIN55,212-2 and JWH015 inhibited fibroblastic and epithelial cell proliferation on day 5. TGF-β1 and TNF-α release increased, while IL-8 release decreased in LL24, LL29, A549 and THP-1 cells in response to administration of WIN55,212-2 and JWH015 at 10-2 mM concentration. CB1R and CB2R antagonists AM251 and AM630, respectively, did not block agonistic responses, suggesting a non-classical CBR mediated pathway. CB2R agonist JWH015 decreased ColI expression from IPF lung fibroblasts LL29 on day 3.Conclusion: These results suggest that CB signaling plays a regulatory role in the progress of pulmonary inflammation and fibrosis and via CBR activation that may offer a potential pharmacological tool for developing antifibrosis therapies.

Author ORCID Identifier

SEVİL KÖSE: 0000-0003-2188-9534

SELİN ÖNEN: 0000-0002-3255-3035

MERVE GİZER: 0000-0003-1911-2363

ESİN BODUROĞLU: 0000-0002-0465-8403

UĞUR GÖNÜLLÜ: 0000-0002-4508-4100

PETEK KORKUSUZ: 0000-0002-7553-3915

DOI

10.55730/1300-0152.2713

Keywords

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

First Page

379

Last Page

389

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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