Sonic hedgehog drives layered double hydroxides-induced acute inflammatory landscape

Autor(es)

Feltran, Georgia da Silva ^[1] ; da Costa Fernandes, Celio Junior ^[1] ; Ferreira, Marcel Rodrigues ^[1] ; Kang, Ha Ram ^[1] ; de Carvalho Bovolato, Ana Livia ^[2] ; Golim, Marjorie de Assis ^[2] ; Deffune, Elenice ^[2] ; Jun Koh, Ivan Hong ^[3] ; Leopoldo Constantino, Vera Regina ^[4] ; Zambuzzi, Willian F. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Paulista, Inst Biociencias, Lab Bioensaios & Dinam Celular, Dept Quim & Bioquim, UNESP, Campus Botucatu, BR-18618970 Sao Paulo - Brazil

^[2] Fac Med Botucatu, Hosp Clin, Hemoctr, Lab Engn Celular, BR-18618688 Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo UNIFESP, Dept Cirurgia, Rua Botucatu 740, BR-04023900 Sao Paulo, SP - Brazil

^[4] Univ Sao Paulo, Inst Quim, Dept Quim Fundamental, Av Prof Linea Prestes 748, BR-05508000 Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: COLLOIDS AND SURFACES B-BIOINTERFACES; v. 174, p. 467-475, FEB 1 2019.
• Citações Web of Science: 2

Resumo

Although layered double hydroxides (LDH) have been listed as promising nanomaterials in human healthcare, very little has been achieved on osteoblast inflammatory signaling. Thus, osteoblasts were challenged with two LDHs (Mg2Al-Cl and Zn2Al-Cl, at 0.002 mg/mL) up to 24 h, establishing an acute inflammatory mechanism, as well as identifying whether Sonic hedgehog (Shh) signaling has an influence. Functional experiments were performed by previously treating (2 h) semiconfluent osteoblast cultures with cyclopamine molecule (cyc), a widely used Shh inhibitor. Considering inflammasome complex, the asc1 gene was significantly up-expressed in response to Zn2Al-Cl - LDHs, as well as the nrlp3 gene. By treating the osteoblast with cyc, the asc1 gene presented an even higher profile. Our results found a down-modulation of major pro-inflammatory cytokines-related genes, when tnfa and il1 beta were significantly down-modulated in response to LDHs. Conversely, anti-inflammatory cytokines were up-modulated considering the same experimental procedures. Except the il6, the other il13,il10, and tgf beta genes were up modulated. Additionally, Shh signaling seems to modulate this repertory as both the il13 and il10 genes were significantly up-modulated when the Shh signaling was inhibited. Altogether, our results reveal for the first time the exigency of Shh-dependent anti-inflammatory signals in LDH-induced osteoblast responses. (AU)

• Processo FAPESP: 11/50318-1 - Desenvolvimento de compostos com interesse farmacológico ou medicinal e de sistemas para seu transporte, detecção e reconhecimento no meio biológico
• Beneficiário: Ana Maria da Costa Ferreira
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 14/22689-3 - Sinalização parácrina mediada por microvesículas e proteínas entre células ósseas e endoteliais durante o desenvolvimento e regeneração do tecido ósseo
• Beneficiário: Willian Fernando Zambuzzi
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores