K Dessalle1, V Narayanan1, S Kyoh1, A Mogas1, A J Halayko2, P Nair3, C J Baglole1, D H Eidelman1, M S Ludwig1, Q Hamid1,4. 1. Meakins-Christie Laboratories, McGill University, Montreal, QC, Canada. 2. Faculty of Medicine, University of Manitoba, Winnipeg, MB, Canada. 3. Firestone Institute for Respiratory Health, St. Joseph's Healthcare and Department of Medicine, McMaster University, Hamilton, ON, Canada. 4. College of Medicine, University of Sharjah, UAE.
Abstract
BACKGROUND: Chronic inflammation, typified by increased expression of IL-17A, together with airway and parenchymal remodelling are features of chronic lung diseases. Emerging evidence suggests that phenotypic heterogeneity of repair and inflammatory capacities of fibroblasts may contribute to the differential structural changes observed in different regions of the lung. OBJECTIVE: To investigate phenotypic differences in parenchymal and bronchial fibroblasts, either in terms of inflammation and remodelling or the ability of these fibroblasts to respond to IL-17A. METHODS: Four groups of primary fibroblasts were used: normal human bronchial fibroblast (NHBF), normal human parenchymal fibroblast (NHPF), COPD human bronchial fibroblast (CHBF) and COPD human parenchymal fibroblast (CHPF). Cytokine and extracellular matrix (ECM) expression were measured at baseline and after stimulation with IL-17A. Actinomycin D was used to measure cytokine mRNA stability. RESULTS: At baseline, we observed higher protein production of IL-6 in NHPF than NHBF, but higher levels of IL-8 and GRO-α in NHBF. IL-17A induced a higher expression of GRO-α (CXCL1) and IL-6 in NHPF than in NHBF, and a higher level of IL-8 expression in NHBF. IL-17A treatment decreased the mRNA stability of IL-6 in NHBF when compared with NHPF. CHPF expressed higher protein levels of fibronectin, collagen-I and collagen-III than CHBF, NHBF and NHPF. IL-17A increased fibronectin and collagen-III protein only in NHPF and collagen-III protein production in CHBF and CHPF. CONCLUSIONS AND CLINICAL RELEVANCE: These findings provide insight into the inflammatory and remodelling processes that may be related to the phenotypic heterogeneity of fibroblasts from airway and parenchymal regions and in their response to IL-17A.
BACKGROUND:Chronic inflammation, typified by increased expression of IL-17A, together with airway and parenchymal remodelling are features of chronic lung diseases. Emerging evidence suggests that phenotypic heterogeneity of repair and inflammatory capacities of fibroblasts may contribute to the differential structural changes observed in different regions of the lung. OBJECTIVE: To investigate phenotypic differences in parenchymal and bronchial fibroblasts, either in terms of inflammation and remodelling or the ability of these fibroblasts to respond to IL-17A. METHODS: Four groups of primary fibroblasts were used: normal human bronchial fibroblast (NHBF), normal human parenchymal fibroblast (NHPF), COPDhuman bronchial fibroblast (CHBF) and COPDhuman parenchymal fibroblast (CHPF). Cytokine and extracellular matrix (ECM) expression were measured at baseline and after stimulation with IL-17A. Actinomycin D was used to measure cytokine mRNA stability. RESULTS: At baseline, we observed higher protein production of IL-6 in NHPF than NHBF, but higher levels of IL-8 and GRO-α in NHBF. IL-17A induced a higher expression of GRO-α (CXCL1) and IL-6 in NHPF than in NHBF, and a higher level of IL-8 expression in NHBF. IL-17A treatment decreased the mRNA stability of IL-6 in NHBF when compared with NHPF. CHPF expressed higher protein levels of fibronectin, collagen-I and collagen-III than CHBF, NHBF and NHPF. IL-17A increased fibronectin and collagen-III protein only in NHPF and collagen-III protein production in CHBF and CHPF. CONCLUSIONS AND CLINICAL RELEVANCE: These findings provide insight into the inflammatory and remodelling processes that may be related to the phenotypic heterogeneity of fibroblasts from airway and parenchymal regions and in their response to IL-17A.
Authors: Tillie-Louise Hackett; Alan J Knox; Rachel L Clifford; Nick Fishbane; Jamie Patel; Julia L MacIsaac; Lisa M McEwen; Andrew J Fisher; Corry-Anke Brandsma; Parameswaran Nair; Michael S Kobor Journal: Clin Epigenetics Date: 2018-03-05 Impact factor: 7.259
Authors: Maria Llamazares-Prada; Elisa Espinet; Vedrana Mijošek; Uwe Schwartz; Pavlo Lutsik; Raluca Tamas; Mandy Richter; Annika Behrendt; Stephanie T Pohl; Naja P Benz; Thomas Muley; Arne Warth; Claus Peter Heußel; Hauke Winter; Jonathan J M Landry; Felix Jf Herth; Tinne Cj Mertens; Harry Karmouty-Quintana; Ina Koch; Vladimir Benes; Jan O Korbel; Sebastian M Waszak; Andreas Trumpp; David M Wyatt; Heiko F Stahl; Christoph Plass; Renata Z Jurkowska Journal: JCI Insight Date: 2021-03-22
Authors: Siti Farah Rahmawati; Maurice Te Velde; Huib A M Kerstjens; Alexander S S Dömling; Matthew Robert Groves; Reinoud Gosens Journal: Front Allergy Date: 2021-08-30
Authors: Rakhee K Ramakrishnan; Khuloud Bajbouj; Saba Al Heialy; Bassam Mahboub; Abdul Wahid Ansari; Ibrahim Y Hachim; Surendra Rawat; Laila Salameh; Mahmood Y Hachim; Ronald Olivenstein; Rabih Halwani; Rifat Hamoudi; Qutayba Hamid Journal: Front Immunol Date: 2020-05-21 Impact factor: 7.561
Authors: Rachel L Clifford; Chen Xi Yang; Nick Fishbane; Jamie Patel; Julia L MacIsaac; Lisa M McEwen; Sean T May; Marcos Castellanos-Uribe; Parameswaran Nair; Ma'en Obeidat; Michael S Kobor; Alan J Knox; Tillie-Louise Hackett Journal: Clin Epigenetics Date: 2020-10-02 Impact factor: 7.259