title: A constitutive endogenous osteopontin production is important for macrophage function and differentiation.
abstract: Macrophages are involved in the pathological process underlying atherosclerosis and constitutively express the multifunctional protein osteopontin which has important exogenous effects on these cells. However, the effect of the endogenous osteopontin expression on macrophage function has been sparsely studied. To shed light on the importance of the endogenous osteopontin expression, RAW 264.7 macrophage-like cells were silenced in osteopontin expression using RNAi. The cells were analysed for basic functions including attachment, migration, apoptosis and for the expression of macrophage differentiation markers and cytokines. The macrophages with silenced osteopontin expression showed impaired migration and an increased rate of serum starvation-induced apoptosis as compared to osteopontin-producing control cells. Furthermore, the cells with silence osteopontin expression had an altered phenotype with monocyte-like characteristics, including decreased expression of macrophage scavenger receptor A type 1. The altered phenotype of these cells could not be reversed by presence of extracellular osteopontin. In addition the cells with silenced osteopontin expression had a lower expression of IL-12 mRNA and the anti-apoptotic Flip mRNA. We conclude that a constitutive endogenous osteopontin production is important for proper basic functions of macrophages and our study indicates that the constitutive osteopontin production is involved in maintaining macrophages in a differentiated phenotype.
authors.affiliation: Department of Experimental Medical Science, Lund University, BMC C12, SE-22184 Lund, Sweden. tobias.nystrom@med.lu.se
authors.forename: Tobias
authors.initials: T
authors.lastname: Nyström
authors.forename: Ponuts
authors.initials: P
authors.lastname: Dunér
authors.forename: Anna
authors.initials: A
authors.lastname: Hultgårdh-Nilsson
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D020869:Gene Expression Profiling; D018960:Hyaluronan Receptors / Q000378:metabolism; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D018960:Hyaluronan Receptors; D034741:RNA, Small Interfering; D053495:Osteopontin; D051057:Proto-Oncogene Proteins c-akt