title: KC chemokine expression by TGF-beta in C3H10T1/2 cells induced towards osteoblasts.
abstract: The effects of TGF-beta on expression of the platelet-derived growth factor-induced KC protein were explored in mouse mesenchymal C3H10T1/2 and pre-osteoblastic MC3T3-E1 cells to identify a potential role for TGF-beta in expression of angiogenic cytokines during osteogenic differentiation. KC is a member of the CXC chemokine family with homology to human IL-8, a potent neutrophilic chemotactic cytokine. TGF-beta treatment results in increased KC mRNA and protein secretion in C3H10T1/2 induced towards the osteoblastic lineage with all-trans-retinoic acid. This is due to up-regulated transcription rather than enhanced mRNA stability. No induction of KC expression was seen in untreated C3H10T1/2 or MC3T3-E1 upon TGF-beta stimulation. Use of the translational inhibitor cycloheximide results in mRNA "superinduction" suggesting other factors are involved that normally function to down-regulate KC expression. TGF-beta-stimulated conditioned media were a potent chemostimulant for human microvascular endothelial cells (HMEC-1). This activity could be inhibited by pre-incubation with anti-KC neutralizing antibodies.
authors.affiliation: Research Service, VA GLAHS, Los Angeles, CA 90073, USA.
authors.forename: D S
authors.initials: DS
authors.lastname: Bischoff
authors.forename: J H
authors.initials: JH
authors.lastname: Zhu
authors.forename: N S
authors.initials: NS
authors.lastname: Makhijani
authors.forename: D T
authors.initials: DT
authors.lastname: Yamaguchi
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D054360:Chemokine CXCL1; D018925:Chemokines; D019743:Chemokines, CXC; D002633:Chemotaxis / Q000187:drug effects; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D054360:Chemokine CXCL1; D018925:Chemokines; D019743:Chemokines, CXC; C475895:Cxcl1 protein, mouse; D016207:Cytokines; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; C074302:keratinocyte-derived chemokines; D014212:Tretinoin