title: Schistosoma mansoni schistosomula reduce E-selectin and VCAM-1 expression in TNF-alpha-stimulated lung microvascular endothelial cells by interfering with the NF-kappaB pathway.
abstract: The recruitment of immune cells into the lungs is a key step in protection against murine schistosomiasis. In this phenomenon, pulmonary (micro)vascular endothelial cells (EC) probably play a central role, by expressing specific adhesion molecules on their surface. Recently, we have shown that Schistosoma mansoni schistosomula, the parasitic stage which resides in the lungs, could activate microvascular EC to acquire an anti-inflammatory phenotype. In the present study, we tested the hypothesis that schistosomula could also regulate the expression of adhesion molecules in vitro by human lung microvascular EC (HMVEC-l) in the present of the pro-inflammatory cytokine TNF-alpha. We found that lipophilic substance(s) present in the excretory/secretory products from schistosomula selectively reduce the TNF-alpha-induced synthesis of E-selectin and VCAM-1 mRNA and proteins without affecting ICAM-1. This inhibitory effect appears to be mediated by a cyclic AMP/protein kinase A (cAMP/PKA) pathway that probably interferes with the NF-kappaB pathway induced by TNF-alpha at the level of the E-selectin promoter, whereas a cAMP-independent pathway appears to operate in VCAM-1 down-modulation. Finally, schistosomula also significantly reduce the VLA-4/VCAM-1-dependent adherence of leukocytes to TNF-alpha-stimulated HMVEC-l. We speculate that this mechanism could represent a new stratagem that parasites may use to escape the immune system by controlling leukocyte recruitment to the lungs.
authors.affiliation: Centre d'Immunologie et de Biologie, Parasitaire INSERM U167, Institut Pasteur de Lille, Lille, France. francois.trottein@pasteur-lille.fr
authors.forename: F
authors.initials: F
authors.lastname: Trottein
authors.forename: S
authors.initials: S
authors.lastname: Nutten
authors.forename: V
authors.initials: V
authors.lastname: Angeli
authors.forename: P
authors.initials: P
authors.lastname: Delerive
authors.forename: E
authors.initials: E
authors.lastname: Teissier
authors.forename: A
authors.initials: A
authors.lastname: Capron
authors.forename: B
authors.initials: B
authors.lastname: Staels
authors.forename: M
authors.initials: M
authors.lastname: Capron
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000276:immunology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases; D019040:E-Selectin / Q000096:biosynthesis* / Q000235:genetics; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology*; D015870:Gene Expression; D018922:HL-60 Cells; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000276:immunology; D008168:Lung / Q000098:blood supply / Q000276:immunology*; D016328:NF-kappa B / Q000276:immunology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000276:immunology; D012333:RNA, Messenger; D016201:Receptors, Lymphocyte Homing / Q000276:immunology; D012550:Schistosoma mansoni / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D019040:E-Selectin; D039041:Integrin alpha4beta1; D016023:Integrins; D016328:NF-kappa B; D012333:RNA, Messenger; D016201:Receptors, Lymphocyte Homing; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D000242:Cyclic AMP; D017346:Protein Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases