TLR7 promotes smoke-induced experimental lung damage through the activity of mast cell tryptase.
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ABSTRACT:
SUBMITTER: Liu G
PROVIDER: S-EPMC10646046 | biostudies-literature | 2023 Nov
REPOSITORIES: biostudies-literature
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TLR7 promotes smoke-induced experimental lung damage through the activity of mast cell tryptase.
Liu Gang G Haw Tatt Jhong TJ Starkey Malcolm R MR Philp Ashleigh M AM Pavlidis Stelios S Nalkurthi Christina C Nair Prema M PM Gomez Henry M HM Hanish Irwan I Hsu Alan Cy AC Hortle Elinor E Pickles Sophie S Rojas-Quintero Joselyn J Estepar Raul San Jose RSJ Marshall Jacqueline E JE Kim Richard Y RY Collison Adam M AM Mattes Joerg J Idrees Sobia S Faiz Alen A Hansbro Nicole G NG Fukui Ryutaro R Murakami Yusuke Y Cheng Hong Sheng HS Tan Nguan Soon NS Chotirmall Sanjay H SH Horvat Jay C JC Foster Paul S PS Oliver Brian Gg BG Polverino Francesca F Ieni Antonio A Monaco Francesco F Caramori Gaetano G Sohal Sukhwinder S SS Bracke Ken R KR Wark Peter A PA Adcock Ian M IM Miyake Kensuke K Sin Don D DD Hansbro Philip M PM
Nature communications 20231114 1
Toll-like receptor 7 (TLR7) is known for eliciting immunity against single-stranded RNA viruses, and is increased in both human and cigarette smoke (CS)-induced, experimental chronic obstructive pulmonary disease (COPD). Here we show that the severity of CS-induced emphysema and COPD is reduced in TLR7-deficient mice, while inhalation of imiquimod, a TLR7-agonist, induces emphysema without CS exposure. This imiquimod-induced emphysema is reduced in mice deficient in mast cell protease-6, or when ...[more]
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Project description:BackgroundMast cells may activate fibroblasts and contribute to remodeling processes in the lung. However, the mechanism behind these actions needs to be further investigated. Fibroblasts are major regulators of on-going remodeling processes. Protease activated receptor 2 (PAR2) expressed by fibroblasts may be activated by serine proteases, such as the mast cell mediator tryptase. The objective in this study was to investigate the effects of mast cells and specifically mast cell tryptase on fibroblast migration and the role of PAR2 activation.MethodsHuman lung fibroblasts (HFL-1) were cultured together with human peripheral blood-derived mast cells or LAD2 mast cells and stimulated with either conditioned medium from LAD2 cells or tryptase. Analyses of immunological stimulation of mast cells by IgE/anti IgE in the co-culture system were also performed. The importance of PAR2 activation by mast cells and mast cell tryptase for the migratory effects of fibroblasts was investigated by pre-treatment with the PAR2 antagonist P2pal-18S. The expression of PAR2 was analyzed on fibroblasts and mast cells.ResultsThe migratory capacity of HFL-1 cells was enhanced by blood-derived mast cells (p < 0.02), LAD2 cells (p < 0.001), conditioned medium (p < 0.05) and tryptase (p < 0.006). P2pal-18S decreased the induced migration caused by mast cells (p < 0.001) and tryptase (p < 0.001) and the expression of PAR2 was verified in HFL-1 cells. Mast cells immunologically stimulated with IgE/Anti IgE had no further effects on fibroblast migration.ConclusionsMast cells and the mast cell mediator tryptase may have crucial roles in inducing lung fibroblast migration via PAR-2 activation, which may contribute to remodeling processes in chronic lung diseases.
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