Bronchial epithelial cells release inflammatory markers linked to airway inflammation and remodeling in response to TLR5 ligand flagellin
Bronchial epithelial cells release inflammatory markers linked to airway inflammation and remodeling in response to TLR5 ligand flagellin
Background/aims: flagellin, which is abundant in gram-negative bacteria, including Pseudomonas, is reported to influence on inflammatory responses in various lung diseases. However, its effect on airway epithelial cells in contribution to asthma pathogenesis is not elucidated yet. We aimed to investigate the effect of TLR5 ligand flagellin on the transcriptomic profile of primary human epithelial cells and to determine the markers of airway inflammation.
Methods: normal human bronchial epithelial (NHBE) cells were grown and differentiated in air-liquid interface (ALI) culture for 14-16 days. The cells were treated with flagellin in vitro at 10 and 100 ng/ml for 3 and 24 h. The conditioned media and cells were harvested to validate inflammatory markers involved in airway inflammation using ELISA, Western blot, and quantitative PCR methods. RNA-sequencing was performed to investigate the transcriptional response to flagellin in ALI-NHBE cells.
Results: altered transcriptional responses to flagellin in differentiated bronchial epithelial cells were determined, including genes encoding chemokines, matrix metalloproteinases, and antimicrobial biomolecules. Pathway analysis of the transcriptionally responsive genes revealed enrichment of signaling pathways. Flagellin induced the mRNA expressions of proinflammatory cytokines and chemokines, and secretion of GM-CSF, CXCL5, CCL5 and CXCL10. Flagellin enhanced the protein expression of MMP-13 in TGF-β1 and TGF-β2 pretreated cell lysates and Wnt/β-catenin signaling.
Conclusions: these findings suggest that flagellin could be a potent inducer of inflammatory markers that may contribute to airway inflammation and remodeling.
Losol, Purevsuren
13912f45-98d6-4aba-b057-0027993de4c7
Ji, Mi-Hong
55e89d09-80e4-40f7-8a91-4343c5e99a25
Kim, Jin Hee
808dcd4f-ab4e-42d0-b2bd-8b6edf07e0c7
Choi, Jun-Pyo
61d10087-78ec-4402-a1a3-d4400e7deaab
Yun, Jeong-Eun
285ca69b-6390-4d6d-b6ed-971cf42c671e
Seo, Jang-Ho
ea896465-d8bd-45a3-a59f-b39ea539db26
Kim, Byung-Keun
1a39e81d-a966-4b61-99f7-9e639b1c08dc
Chang, Yoon-Seok
6c517880-794d-4b83-926d-1940310e2ce5
Kim, Sae-Hoon
81a4a809-ddb7-4291-897f-62f5177a49ac
10 June 2023
Losol, Purevsuren
13912f45-98d6-4aba-b057-0027993de4c7
Ji, Mi-Hong
55e89d09-80e4-40f7-8a91-4343c5e99a25
Kim, Jin Hee
808dcd4f-ab4e-42d0-b2bd-8b6edf07e0c7
Choi, Jun-Pyo
61d10087-78ec-4402-a1a3-d4400e7deaab
Yun, Jeong-Eun
285ca69b-6390-4d6d-b6ed-971cf42c671e
Seo, Jang-Ho
ea896465-d8bd-45a3-a59f-b39ea539db26
Kim, Byung-Keun
1a39e81d-a966-4b61-99f7-9e639b1c08dc
Chang, Yoon-Seok
6c517880-794d-4b83-926d-1940310e2ce5
Kim, Sae-Hoon
81a4a809-ddb7-4291-897f-62f5177a49ac
Losol, Purevsuren, Ji, Mi-Hong, Kim, Jin Hee, Choi, Jun-Pyo, Yun, Jeong-Eun, Seo, Jang-Ho, Kim, Byung-Keun, Chang, Yoon-Seok and Kim, Sae-Hoon
(2023)
Bronchial epithelial cells release inflammatory markers linked to airway inflammation and remodeling in response to TLR5 ligand flagellin.
World Allergy Organization Journal, 16 (6), [100786].
(doi:10.1016/j.waojou.2023.100786).
Abstract
Background/aims: flagellin, which is abundant in gram-negative bacteria, including Pseudomonas, is reported to influence on inflammatory responses in various lung diseases. However, its effect on airway epithelial cells in contribution to asthma pathogenesis is not elucidated yet. We aimed to investigate the effect of TLR5 ligand flagellin on the transcriptomic profile of primary human epithelial cells and to determine the markers of airway inflammation.
Methods: normal human bronchial epithelial (NHBE) cells were grown and differentiated in air-liquid interface (ALI) culture for 14-16 days. The cells were treated with flagellin in vitro at 10 and 100 ng/ml for 3 and 24 h. The conditioned media and cells were harvested to validate inflammatory markers involved in airway inflammation using ELISA, Western blot, and quantitative PCR methods. RNA-sequencing was performed to investigate the transcriptional response to flagellin in ALI-NHBE cells.
Results: altered transcriptional responses to flagellin in differentiated bronchial epithelial cells were determined, including genes encoding chemokines, matrix metalloproteinases, and antimicrobial biomolecules. Pathway analysis of the transcriptionally responsive genes revealed enrichment of signaling pathways. Flagellin induced the mRNA expressions of proinflammatory cytokines and chemokines, and secretion of GM-CSF, CXCL5, CCL5 and CXCL10. Flagellin enhanced the protein expression of MMP-13 in TGF-β1 and TGF-β2 pretreated cell lysates and Wnt/β-catenin signaling.
Conclusions: these findings suggest that flagellin could be a potent inducer of inflammatory markers that may contribute to airway inflammation and remodeling.
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Accepted/In Press date: 16 May 2023
e-pub ahead of print date: 10 June 2023
Published date: 10 June 2023
Identifiers
Local EPrints ID: 507159
URI: http://eprints.soton.ac.uk/id/eprint/507159
ISSN: 1939-4551
PURE UUID: 397304b7-d451-417f-974c-4f139b47eb60
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Date deposited: 28 Nov 2025 17:32
Last modified: 29 Nov 2025 03:07
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Author:
Purevsuren Losol
Author:
Mi-Hong Ji
Author:
Jin Hee Kim
Author:
Jun-Pyo Choi
Author:
Jeong-Eun Yun
Author:
Jang-Ho Seo
Author:
Byung-Keun Kim
Author:
Yoon-Seok Chang
Author:
Sae-Hoon Kim
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