title: Monocytes from sickle cell disease patients induce differential pulmonary endothelial gene expression via activation of NF-κB signaling pathway.
abstract: Monocyte-endothelial interactions play an important role in inflammatory diseases and may modulate vasculopathy in sickle cell disease, a disorder with an important inflammatory component. We co-incubated normal and sickle monocytes, lymphocytes and TNF-α with pulmonary microvascular and arterial endothelial cells and compared the expression of genes coding for adhesion molecules and cytokines that might contribute to sickle vasoocclusion. Monocyte-endothelial cell co-incubation resulted in up-regulation of L-selectin, E-selectin, VCAM-1, ICAM-1, MCP-1, MMP-1, TNF-α, IL-6 and IL-1β and down-regulation of eNOS. Lymphocyte-endothelial cell co-incubations, induced similar effects restricted to pulmonary artery endothelial cells. TNF-α had similar effects on the endothelial cells as monocytes did, however monocyte induced gene expression in endothelial cells was not TNF-α dependent but was regulated through the NF-κB pathway. Sickle monocytes lead to altered expression of L-selectin, MCP-1 and MMP-1 in pulmonary vascular endothelium when compared with normal monocytes. The gene expression changes we observed could reflect pathological events of sickle vasoocclusion.
authors.affiliation: Center of Excellence in Sickle Cell Disease and Division of Hematology/Oncology, Department of Medicine, Boston University School of Medicine, 88-East Newton St., Boston, MA 02118, USA. ssafaya@bu.edu
authors.forename: Surinder
authors.initials: S
authors.lastname: Safaya
authors.forename: Martin H
authors.initials: MH
authors.lastname: Steinberg
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Klings
mesh_terms: D000755:Anemia, Sickle Cell / Q000097:blood / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000235:genetics; D002450:Cell Communication; D002460:Cell Line; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000235:genetics; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D011651:Pulmonary Artery / Q000166:cytology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000494:pharmacology
chemical_list: D015815:Cell Adhesion Molecules; D016207:Cytokines; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D052250:Nitric Oxide Synthase Type III