PMID- 35832729 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220716 IS - 2001-8525 (Print) IS - 2001-8525 (Electronic) IS - 2001-8525 (Linking) VI - 9 IP - 1 DP - 2022 TI - Cellular mechanisms involved in the pathogenesis of airway remodeling in chronic lung disease. PG - 2097377 LID - 10.1080/20018525.2022.2097377 [doi] LID - 2097377 AB - BACKGROUND: Airway epithelial cells and lung fibroblasts play an important role in the development of chronic lung disease, but the exact mechanisms responsible have not been clarified. Our objective was to investigate the involvement of these cells in the inflammatory response associated to chronic lung disease. METHODS: Human lung fibroblasts and airway epithelial cells were challenged with Interleukin-1beta and hypoxia, and with inhibitory (simvastatin) stimuli of the inflammatory response. Expression of markers of local inflammation ((IL-8, monocyte chemoattractant protein-1 (MCP-1), factor-kappaB1 (NF-kappaB1)), systemic inflammation ((C-reactive protein (CRP) and serum amyloid A (SAA)) and proteases matrix metalloproteinase (MMP) 9 and 12 were assessed by PCR and ELISA. Apoptosis/necrosis was analyzed by flow cytometry. RESULTS: Our results showed that the lung fibroblasts had a higher expression of local and systemic inflammation and protease activity markers when they were treated with IL-1beta compared to airway epithelial cells. Under hypoxic conditions, we observed a decrease in systemic inflammation in lung fibroblasts, which was further attenuated by simvastatin. CONCLUSION: The lung fibroblasts seem to be the main initially stimulated cells that could potentially trigger the inflammatory response, and be responsible for the eventual onset of chronic lung disease. The involvement of IL-1ss stimulation in systemic inflammatory and proteinase imbalance biomarkers is higher in lung fibroblasts. Apoptosis is not a predominant mechanism in these cells. CI - (c) 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. FAU - Arellano-Orden, E AU - Arellano-Orden E AD - Unidad Medico Quirurgica de Enfermedades Respiratorias, Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocio/Universidad de SevillaUnidad Medico Quirurgica de Enfermedades Respiratorias,Quirurgica, Seville, Spain. AD - CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain. FAU - Calero Acuna, C AU - Calero Acuna C AD - Unidad Medico Quirurgica de Enfermedades Respiratorias, Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocio/Universidad de SevillaUnidad Medico Quirurgica de Enfermedades Respiratorias,Quirurgica, Seville, Spain. AD - CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain. FAU - Sanchez-Lopez, V AU - Sanchez-Lopez V AD - Unidad Medico Quirurgica de Enfermedades Respiratorias, Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocio/Universidad de SevillaUnidad Medico Quirurgica de Enfermedades Respiratorias,Quirurgica, Seville, Spain. AD - CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain. FAU - Lopez Ramirez, C AU - Lopez Ramirez C AD - Unidad Medico Quirurgica de Enfermedades Respiratorias, Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocio/Universidad de SevillaUnidad Medico Quirurgica de Enfermedades Respiratorias,Quirurgica, Seville, Spain. AD - CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain. FAU - Otero-Candelera, R AU - Otero-Candelera R AD - Unidad Medico Quirurgica de Enfermedades Respiratorias, Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocio/Universidad de SevillaUnidad Medico Quirurgica de Enfermedades Respiratorias,Quirurgica, Seville, Spain. AD - CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain. FAU - Marin-Hinojosa, C AU - Marin-Hinojosa C AD - Unidad Medico Quirurgica de Enfermedades Respiratorias, Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocio/Universidad de SevillaUnidad Medico Quirurgica de Enfermedades Respiratorias,Quirurgica, Seville, Spain. AD - CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain. FAU - Lopez Campos, Jl AU - Lopez Campos J AUID- ORCID: 0000-0003-1703-1367 AD - Unidad Medico Quirurgica de Enfermedades Respiratorias, Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocio/Universidad de SevillaUnidad Medico Quirurgica de Enfermedades Respiratorias,Quirurgica, Seville, Spain. AD - CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain. LA - eng PT - Journal Article DEP - 20220708 PL - United States TA - Eur Clin Respir J JT - European clinical respiratory journal JID - 101662134 PMC - PMC9272929 OTO - NOTNLM OT - Chronic lung disease OT - human airway epithelial cells OT - human lung fibroblasts OT - inflammatory response OT - pathogenesis and simvastatin COIS- No potential conflict of interest was reported by the author(s). EDAT- 2022/07/15 06:00 MHDA- 2022/07/15 06:01 PMCR- 2022/07/08 CRDT- 2022/07/14 02:28 PHST- 2022/07/14 02:28 [entrez] PHST- 2022/07/15 06:00 [pubmed] PHST- 2022/07/15 06:01 [medline] PHST- 2022/07/08 00:00 [pmc-release] AID - 2097377 [pii] AID - 10.1080/20018525.2022.2097377 [doi] PST - epublish SO - Eur Clin Respir J. 2022 Jul 8;9(1):2097377. doi: 10.1080/20018525.2022.2097377. eCollection 2022.