title: Dentin sialoprotein and phosphoprotein induce neutrophil recruitment: a mechanism dependent on IL-1beta, TNF-beta, and CXC chemokines.
abstract: Dentin is a reservoir of several potentially active molecules, and dentin sialoprotein (DSP) and dentin phosphoprotein (DPP) are the two major non-collagenous proteins. It has been established that dentin molecules are released as a consequence of osteoclast action during the resorption process. Along with osteoclasts, inflammatory cells seem to play an important role at sites of root resorption. Although the role of dentin molecules in dentinogenesis is well known, their role in pathological processes associated with dentin matrix dissolution is unclear. Recent studies have suggested that dentin components may function as chemotactic and activator signals for inflammatory cells at these sites. Herein we present evidence that demineralized dentin crude extract, DSP, and DPP induced doseand time-dependent neutrophil migration into the peritoneal cavity of mice and that this activity was inhibited by dexamethasone, but not by indomethacin or MK886. The blockade of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) receptors inhibited neutrophil accumulation. The neutrophil migration was also diminished in the absence of the chemokines cytokine-induced neutrophil chemoattractant (KC) and macrophage inflammatory protein-2 (MIP-2), but not in the absence of macrophage inflammatory protein-1alpha (MIP-1alpha). These results demonstrate that dentin induces neutrophil migration via the synthesis of IL-1beta, TNF-alpha, and chemokines and they suggest that dentin matrix proteins may have an active role in inflammatory cell recruitment during pathological processes associated with dentin and bone matrix dissolution.
authors.affiliation: Department of Stomatology, Faculty of Dentistry of Bauru, University of São Paulo, São Paulo, Brazil. tarcilia@zipmail.com.br
authors.forename: T A
authors.initials: TA
authors.lastname: Silva
authors.forename: V S
authors.initials: VS
authors.lastname: Lara
authors.forename: J S
authors.initials: JS
authors.lastname: Silva
authors.forename: G P
authors.initials: GP
authors.lastname: Garlet
authors.forename: W T
authors.initials: WT
authors.lastname: Butler
authors.forename: F Q
authors.initials: FQ
authors.lastname: Cunha
mesh_terms: D000818:Animals; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines / Q000378:metabolism*; D019743:Chemokines, CXC / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003804:Dentin / Q000737:chemistry*; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016326:Extracellular Matrix Proteins / Q000494:pharmacology; D007375:Interleukin-1 / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000187:drug effects* / Q000502:physiology; D010750:Phosphoproteins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012795:Sialoglycoproteins / Q000494:pharmacology*; D014020:Tissue Extracts / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics
chemical_list: D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines; D019743:Chemokines, CXC; D016326:Extracellular Matrix Proteins; D007375:Interleukin-1; D019402:Macrophage Inflammatory Proteins; D010750:Phosphoproteins; D012795:Sialoglycoproteins; D014020:Tissue Extracts; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone