title: Expression and function of the homeostatic molecule Del-1 in endothelial cells and the periodontal tissue.
abstract: Developmental endothelial locus-1 (Del-1) is an endothelial cell-secreted protein that limits the recruitment of neutrophils by antagonizing the interaction between the LFA-1 integrin on neutrophils and the intercellular adhesion molecule (ICAM)-1 on endothelial cells. Mice with genetic or age-associated Del-1 deficiency exhibit increased neutrophil infiltration in the periodontium resulting in inflammatory bone loss. Here we investigated additional novel mechanisms whereby Del-1 could interfere with neutrophil recruitment and inflammation. Treatment of human endothelial cells with Del-1 did not affect the expression of endothelial molecules involved in the leukocyte adhesion cascade (ICAM-1, VCAM-1, and E-selectin). Moreover, genetic or age-associated Del-1 deficiency did not significantly alter the expression of these adhesion molecules in the murine periodontium, further ruling out altered adhesion molecule expression as a mechanism whereby Del-1 regulates leukocyte recruitment. Strikingly, Del-1 inhibited ICAM-1-dependent chemokine release (CXCL2, CCL3) by neutrophils. Therefore, Del-1 could potentially suppress the amplification of inflammatory cell recruitment mediated through chemokine release by infiltrating neutrophils. Interestingly, Del-1 was itself regulated by inflammatory stimuli, which generally exerted opposite effects on adhesion molecule expression. The reciprocal regulation between Del-1 and inflammation may contribute to optimally balance the protective and the potentially harmful effects of inflammatory cell recruitment.
authors.affiliation: Department of Microbiology, School of Dental Medicine, University of Pennsylvania, 240 South 40th Street, Philadelphia, PA 19104, USA.
authors.forename: Jieun
authors.initials: J
authors.lastname: Shin
authors.affiliation: Department of Microbiology, School of Dental Medicine, University of Pennsylvania, 240 South 40th Street, Philadelphia, PA 19104, USA.
authors.forename: Kavita B
authors.initials: KB
authors.lastname: Hosur
authors.affiliation: Department of Microbiology, School of Dental Medicine, University of Pennsylvania, 240 South 40th Street, Philadelphia, PA 19104, USA ; Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Kalyani
authors.initials: K
authors.lastname: Pyaram
authors.affiliation: Oral Health and Systemic Disease Research Group, University of Louisville School of Dentistry, Louisville, KY 40292, USA.
authors.forename: Ravi
authors.initials: R
authors.lastname: Jotwani
authors.affiliation: Oral Health and Systemic Disease Research Group, University of Louisville School of Dentistry, Louisville, KY 40292, USA.
authors.forename: Shuang
authors.initials: S
authors.lastname: Liang
authors.affiliation: Division of Vascular Inflammation, Diabetes and Kidney, Department of Medicine, Technical University Dresden, 01307 Dresden, Germany ; Department of Clinical Pathobiochemistry and Institute for Clinical Chemistry and Laboratory Medicine, Technical University Dresden, 01307 Dresden, Germany.
authors.forename: Triantafyllos
authors.initials: T
authors.lastname: Chavakis
authors.affiliation: Department of Microbiology, School of Dental Medicine, University of Pennsylvania, 240 South 40th Street, Philadelphia, PA 19104, USA.
authors.forename: George
authors.initials: G
authors.lastname: Hajishengallis
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D018925:Chemokines / Q000096:biosynthesis; D042783:Endothelial Cells / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000378:metabolism; D010024:Osteoporosis / Q000235:genetics / Q000378:metabolism; D010518:Periodontitis / Q000235:genetics / Q000276:immunology; D010519:Periodontium / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D018925:Chemokines; C110183:EDIL3 protein, human; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1