In vitro expression of Fas and CD40 and induction of apoptosis in human cystic fibrosis airway epithelial cells

Amsellem, Carole; Durieu, I.; Chambe, Marie-Thérèse; Peyrol, S; Pachéco, Yves

doi:10.1053/rmed.2001.1257

Cited by 14 publications

(8 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We indeed observed increased virus-induced cytotoxicity due to necrosis in CF cells. Our findings are consistent with the concept of increased epithelial cell death in CF, also described by SUTANTO et al [9], AMSELLEM et al [27] and DURIEU et al [28], suggesting increased susceptibility of the CF airway epithelium towards toxic effects of respiratory viruses. Chronic inflammatory stimulation, as seen in the context of bacterial colonisation, could lead to such increased susceptibility to cytotoxic stimuli.…”

Section: Discussionsupporting

confidence: 93%

Lack of an exaggerated inflammatory response on virus infection in cystic fibrosis

Kieninger¹,

Vareille²,

Kopf³

et al. 2011

European Respiratory Journal

View full text Add to dashboard Cite

Respiratory virus infections play an important role in cystic fibrosis (CF) exacerbations, but underlying pathophysiological mechanisms are poorly understood. We aimed to assess whether an exaggerated inflammatory response of the airway epithelium on virus infection could explain the increased susceptibility of CF patients towards respiratory viruses.We used primary bronchial and nasal epithelial cells obtained from 24 healthy control subjects and 18 CF patients. IL-6, IL-8/CXCL8, IP-10/CXCL10, MCP-1/CCL2, RANTES/CCL5 and GRO-a/ CXCL1 levels in supernatants and mRNA expression in cell lysates were measured before and after infection with rhinoviruses (RV-16 and RV-1B) and RSV. Cytotoxicity was assessed by lactate dehydrogenate assay and flow cytometry.All viruses induced strong cytokine release in both control and CF cells. The inflammatory response on virus infection was heterogeneous and depended on cell type and virus used, but was not increased in CF compared with control cells. On the contrary, there was a marked trend towards lower cytokine production associated with increased cell death in CF cells.An exaggerated inflammatory response to virus infection in bronchial epithelial cells does not explain the increased respiratory morbidity after virus infection in CF patients.

show abstract

Section: Discussionsupporting

confidence: 93%

Lack of an exaggerated inflammatory response on virus infection in cystic fibrosis

Kieninger¹,

Vareille²,

Kopf³

et al. 2011

European Respiratory Journal

View full text Add to dashboard Cite

show abstract

“…This observation is consistent with previous studies showing CD40 expression on other epithelial cell types [13,15,16,18]. CD40 signalling is rather complex as it involves protein tyrosine kinases, phosphoinositide-3 kinase, phospholipase Cγ2 and serine/ threonine kinases.…”

Section: Discussionsupporting

confidence: 93%

“…In addition, duct cells were shown to express CD14, a pattern recognition receptor [11,12] that might allow duct cells to respond to microbial products. In renal, airway or intrahepatic epithelial cells, membrane expression of CD40 molecules was found to transduce activation signals upon interaction with CD154, the CD40 ligand [13,14,15,16,17,18]. CD40 is a member of the TNF-receptor family, and was initially described on B cells but subsequently found on a wide variety of cell types including activated monocytes, dendritic cells, endothelial cells, epithelial cells and fibroblasts [19,20,21].…”

Section: Introductionmentioning

confidence: 99%

CD40 expression on human pancreatic duct cells: role in nuclear factor-kappa B activation and production of pro-inflammatory cytokines

Vosters

Beuneu

Nagy³

et al. 2004

Diabetologia

View full text Add to dashboard Cite

Aims/hypothesis. Human pancreatic duct cells are closely associated with islet beta cells, and contaminate islet suspensions transplanted in Type 1 diabetes mellitus patients. Activated duct cells produce cytotoxic mediators and possibly contribute to the pathogenesis of Type 1 diabetes mellitus or islet graft rejection. As CD40 transduces activation signals involved in inflammatory and immune disorders, we investigated CD40 expression on duct cells and their response to CD40 engagement. Methods. CD40 expression on human pancreatic duct cells was analysed by flow cytometry and immunohistochemical analyses. To assess the function of CD40 expression on duct cells, activation of the transcription factor nuclear factor-kappa B was determined using electrophoretic mobility shift assay and ELISA. Cytokine mRNA levels were quantified by real-time RT-PCR, and protein levels by Luminex technology. Results. Isolated human pancreatic duct cells and Capan-2 cell lines were found to express constitutively CD40. The expression of CD40 on duct cells was confirmed in vivo on human normal and pathological pancreatic specimens. CD40 ligation on Capan-2 cells induced rapid nuclear factor-kappa B activation, and supershift assays demonstrated that p50/p65 heterodimers and p50/p50 homodimers were present in the activated complexes in the nucleus. This activation was accompanied by tumour necrosis factor-α and interleukin-1β mRNA accumulation. Tumour necrosis factor-α protein secretion was confirmed in CD40-activated Capan-2 cells and in isolated human pancreatic duct cells. Conclusions/interpretation. Interaction between activated T lymphocytes expressing CD40 ligand and duct cells expressing CD40 may contribute to the immune responses involved in Type 1 diabetes mellitus and islet graft rejection. Interfering with CD40-mediated duct cell activation could alleviate beta cell damage of immune origin.

show abstract

“…Ligating CD95 induces apoptosis (as expected) in normal tracheal epithelial cell lines but increased apoptosis in the CF-derived cell line CFT-2 [183]. The Pseudomonas aeruginosa strain PAO1 induces apoptosis, as demonstrated by TUNEL labeling, in about 10% of primary epithelial cells over 8 hr of exposure but 50% in the 9HTEo-transformed cell line that lacks tight junctions [184]; treating another transformed cell line, 16HBE14o- that has high-quality tight junctions, with EGTA made them more susceptible to PAO1-induced apoptosis.…”

Section: Apoptosis In Airway Epithelium In Diseasementioning

confidence: 69%

Apoptosis and the Airway Epithelium

White

2011

Journal of Allergy

View full text Add to dashboard Cite

The airway epithelium functions as a barrier and front line of host defense in the lung. Apoptosis or programmed cell death can be elicited in the epithelium as a response to viral infection, exposure to allergen or to environmental toxins, or to drugs. While apoptosis can be induced via activation of death receptors on the cell surface or by disruption of mitochondrial polarity, epithelial cells compared to inflammatory cells are more resistant to apoptotic stimuli. This paper focuses on the response of airway epithelium to apoptosis in the normal state, apoptosis as a potential regulator of the number and types of epithelial cells in the airway, and the contribution of epithelial cell apoptosis in important airways diseases.

show abstract

In vitro expression of Fas and CD40 and induction of apoptosis in human cystic fibrosis airway epithelial cells

Cited by 14 publications

References 26 publications

Lack of an exaggerated inflammatory response on virus infection in cystic fibrosis

Lack of an exaggerated inflammatory response on virus infection in cystic fibrosis

CD40 expression on human pancreatic duct cells: role in nuclear factor-kappa B activation and production of pro-inflammatory cytokines

Apoptosis and the Airway Epithelium

Contact Info

Product

Resources

About