Tracheal Smooth Muscle Cells Stimulated by Stem Cell Factor-c-Kit Coordinate the Production of Transforming Growth Factor-1 and Fibroblast Growth Factor-2 Mediated by Chemokine (C-C Motif) Ligand 3

Autor(es)

Farias de Oliveira, Luis Cezar ^[1] ; Danilucci, Tais Marolato ^[1] ; Chaves-Neto, Antonio Hernandes ^[1] ; Campanelli, Ana Paula ^[2] ; Cardoso da Silva, Tereza Cristina ^[3] ; Penha Oliveira, Sandra Helena ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Paulista UNESP, Programa Posgrad Multictr Ciencias Fisiol SBFis, Dept Basic Sci, Sch Dent Aracatuba, Rua Jose Bonifacio 1193, BR-16015050 Aracatuba, SP - Brazil

^[2] Univ Sao Paulo, Sch Dent Bauru, Dept Biol Sci, Bauru - Brazil

^[3] Univ Estadual Paulista UNESP, Sch Med Vet Aracatuba, Lab Anim Virol & Cell Culture, Aracatuba - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF INTERFERON AND CYTOKINE RESEARCH; v. 36, n. 6, p. 401-411, JUN 2016.
• Citações Web of Science: 2

Resumo

The aim of this study was to evaluate the mechanism involved in the stem cell factor (SCF)-induced production of fibroblast growth factor-2 (FGF-2), transforming growth factor-1 (TGF-1), and chemokine (C-C motif) ligand 3 (CCL3) in tracheal smooth muscle cells (tSMCs) and the signaling pathway involved in the process. tSMC primary cultures were stimulated with SCF and evaluated at 24h. Cells treated with specific antibodies did not show any immunolabeling for cytokeratin or fibroblast activation protein, but were positive for -smooth muscle actin, indicating the purity of the primary cell line. Western blot analysis showed constitutive phosphorylation of c-Kit, as well as increased total protein and phosphorylated c-Kit levels in tSMCs after SCF stimulation. Flow cytometry analysis also showed an increase in cell-surface c-Kit expression in the presence of SCF. SCF induced TGF- mRNA expression in tSMCs, as well as the production of TGF-1, CCL3, and FGF-2. Pretreatment with anti-CCL3 antibody blocked TGF-1 expression and partially inhibited FGF-2 production. On the other hand, anti-c-Kit antibody blocked TGF-1 expression and FGF-2 production. Thus, TGF-1 and FGF-2 production were mediated by CCL3 production through c-Kit. Pretreatment with mitogen-activated protein kinase kinase 1, p38, and Jun N-terminal kinase inhibitors showed that the effects mediated by SCF were involved with the modulation of mitogen-activated protein kinase (MAPK) pathways. Development of inhibitors targeting CCL3 through MAPK activation could thus be an attractive strategy to inhibit tSMC activation during asthma. (AU)

• Processo FAPESP: 06/59794-2 - Efeito da hipertensão sobre a atividade funcional de neutrófilos, reabsorção óssea e produção de proteína C reativa por ratos espontaneamente hipertensos submetidos à doença periodontal
• Beneficiário: Sandra Helena Penha de Oliveira
• Modalidade de apoio: Auxílio à Pesquisa - Regular