Aryl hydrocarbon receptor–ligand axis mediates pulmonary fibroblast migration and differentiation through increased arachidonic acid metabolism

Autor: Jau-Ling Suen, Hsin Ting Lin, Chau-Chyun Sheu, Kazunari K. Yokoyama, Shau Ku Huang, Hsiang Han Su, Chih Mei Cheng
Rok vydání: 2016
Předmět:
0301 basic medicine
medicine.medical_specialty
Polychlorinated Dibenzodioxins
Arachidonic Acids
Biology
Toxicology
Leukotriene B4
Dinoprostone
Calcium in biology
Cell Line
Fibroblast migration
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Downregulation and upregulation
Cell Movement
Genes
Reporter
Internal medicine
medicine
Humans
RNA
Small Interfering
Promoter Regions
Genetic
Fibroblast
Lung
Transcription factor
Cytoskeleton
Cell Proliferation
Arachidonate 5-Lipoxygenase
Cell Differentiation
Cell migration
Fibroblasts
Aryl hydrocarbon receptor
Actins
Up-Regulation
Cell biology
030104 developmental biology
Endocrinology
medicine.anatomical_structure
Receptors
Aryl Hydrocarbon
chemistry
Cyclooxygenase 2
030220 oncology & carcinogenesis
biology.protein
Pyrazoles
Arachidonic acid
Azo Compounds
Signal Transduction
Zdroj: Toxicology. 370:116-126
ISSN: 0300-483X
DOI: 10.1016/j.tox.2016.09.019
Popis: Pulmonary fibroblast migration and differentiation are critical events in fibrogenesis; meanwhile, fibrosis characterizes the pathology of many respiratory diseases. The role of aryl hydrocarbon receptor (AhR), a unique cellular chemical sensor, has been suggested in tissue fibrosis, but the mechanisms through which the AhR-ligand axis influences the fibrotic process remain undefined. In this study, the potential impact of the AhR-ligand axis on pulmonary fibroblast migration and differentiation was analyzed using human primary lung fibroblasts HFL-1 and CCL-202 cells. Boyden chamber-based cell migration assay showed that activated AhR in HFL-1cells significantly enhanced cell migration in response to 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD), and a known AhR antagonist, CH223191, inhibited its migratory activity. Furthermore, the calcium mobilization and subsequent upregulated expression of arachidonic acid metabolizing enzymes, including cyclooxygenase2 (COX-2) and 5-lipoxygenase (5-LOX), were observed in TCDD-treated HFL-1 cells, concomitant with elevated levels of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) secretion. Also, significantly increased expression of α-smooth muscle actin α-SMA), a fibroblast differentiation marker, was also noted in TCDD-treated HFL-1 cells (p
Databáze: OpenAIRE
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