Pro-inflammatory effects of extracellular Hsp70 and cigarette smoke in primary airway epithelial cells from COPD patients

Autor: Lada Rumora, Andrea Hulina-Tomašković, Marnix R. Jonker, Irene H. Heijink, Anita Somborac-Bačura, Marija Grdić Rajković
Přispěvatelé: Groningen Research Institute for Asthma and COPD (GRIAC)
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Male
0301 basic medicine
medicine.medical_treatment
HSP27
Pharmacology
Biochemistry
Pulmonary Disease
Chronic Obstructive
Medicine
ACTIVATED PROTEIN-KINASE
Cigarette smoke
General Medicine
3. Good health
RECEPTORS
Cytokine
Female
Signal transduction
medicine.symptom
Extracellular Hsp70
EXPRESSION
p38 mitogen-activated protein kinases
Inflammation
Respiratory Mucosa
SIGNAL-TRANSDUCTION PATHWAY
extracellular Hsp70
cigarette smoke
COPD
inflammation
03 medical and health sciences
HEAT-SHOCK-PROTEIN-70
Immune system
parasitic diseases
COPD
Humans
HSP70 Heat-Shock Proteins
RELEASE
030102 biochemistry & molecular biology
Interleukin-6
business.industry
Interleukin-8
Epithelial Cells
Toll-Like Receptor 2
respiratory tract diseases
Toll-Like Receptor 4
CYTOKINE
TLR2
030104 developmental biology
TLR4
Tobacco Smoke Pollution
Cytokine secretion
business
LUNG
RESPONSES
Zdroj: BIOCHIMIE, 156, 47-58. ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
ISSN: 0300-9084
DOI: 10.1016/j.biochi.2018.09.010
Popis: Extracellular Hsp70 (eHsp70) can activate immune cells via Toll-like receptors (TLR) 2 and 4, and induce cytokine synthesis. The aim of this study was to explore inflammation-associated effects of eHsp70 alone and in combination with cigarette smoke extract (CSE) in primary bronchial epithelial cells.We assessed IL-6 and IL-8 concentrations, TLR2, TLR4 and Hsp70 mRNA expressions, and mitogen-activated protein kinases (MAPKs) activation induced by recombinant human (rh) Hsp70, CSE or their combinations in normal human bronchial epithelial cells (NHBE) obtained commercially, and primary bronchial epithelial cells isolated from non-COPD lung donors (PBEC) or COPD patients (PBEC COPD).Baseline levels of IL-6 and IL-8 were significantly higher in PBEC COPD than in non-COPD PBECs. Upon rhHsp70 stimulation, IL-6 and IL-8 were significantly increased, with the strongest response in COPD-derived PBECs. CSE alone elevated cytokine secretion in all examined cells. rhHsp70 and CSE had antagonistic interactions on IL-8 release in PBECs from COPD patients, while the addition of rhHsp70 further increased CSE-induced IL-6 secretion in NHBE cells. rhHsp70 and CSE alone decreased TLR2 and TLR4 mRNA expression in COPD-derived PBECs. In non-COPD PBECs, combined treatments decreased only TLR2 mRNA expression. Hsp70 mRNA expression, as indicator of intracellular Hsp70, which may have anti-inflammatory effects, was reduced in COPD-derived cells upon exposure to CSE and rhHsp70 alone, but not with their combinations. Contrary to this, in PBECs from lung donors only combined treatments supressed Hsp70 gene expression. CSE activated JNK and p38 MAPKs, while rhHsp70 increased activation of c-Jun kinase in NHBE cells.Collectively, both eHsp70 and CSE induce pro-inflammatory responses in PBECs from non-COPD as well as COPD donors, but in combination antagonistic effects were observed in COPD-derived cells. These effects may be related to the regulation of TLR2/4 and might lead to modulation of inflammation with possible deleterious consequences for COPD patients. (C) 2018 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.
Databáze: OpenAIRE
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