Doxycycline Suppresses Microglial Activation by Inhibiting the p38 MAPK and NF-kB Signaling Pathways

Autor(es)

Santa-Cecilia, Flavia V. ^{[1, 2]} ; Socias, Benjamin ^[2] ; Ouidja, Mohand O. ^[2] ; Sepulveda-Diaz, Julia E. ^[2] ; Acuna, Leonardo ^{[1, 2, 3, 4]} ; Silva, Rangel L. ^[1] ; Michel, Patrick P. ^[2] ; Del-Bel, Elaine ^[5] ; Cunha, Thiago M. ^[1] ; Raisman-Vozari, Rita ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Ave Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Paris 06, Univ Paris 04, INSERM, CNRS, UM75, U1127, UMR 7225, Inst Cerveau & Moelle Epinier, Paris - France

^[3] INSIBIO CONICET UNT, Inst Super Invest Biol, San Miguel De Tucuman, Tucuman - Argentina

^[4] UNT, Fac Bioquim Quim & Farm, Inst Quim Biol Dr Bernabe Bloj, San Miguel De Tucuman, Tucuman - Argentina

^[5] Univ Sao Paulo, Dept Morphol Physiol & Pathol, Sch Odontol Ribeirao Preto FORP, BR-14049900 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: NEUROTOXICITY RESEARCH; v. 29, n. 4, p. 447-459, MAY 2016.
• Citações Web of Science: 34

Resumo

In neurodegenerative diseases, the inflammatory response is mediated by activated glial cells, mainly microglia, which are the resident immune cells of the central nervous system. Activated microglial cells release proinflammatory mediators and neurotoxic factors that are suspected to cause or exacerbate these diseases. We recently demonstrated that doxycycline protects substantia nigra dopaminergic neurons in an animal model of Parkinson's disease. This effect was associated with a reduction of microglial cell activation, which suggests that doxycycline may operate primarily as an anti-inflammatory drug. In the present study, we assessed the anti-inflammatory potential of doxycycline using lipopolysaccharide (LPS)-activated primary microglial cells in culture as a model of neuroinflammation. Doxycycline attenuated the expression of key activation markers in LPS-treated microglial cultures in a concentration-dependent manner. More specifically, doxycycline treatment lowered the expression of the microglial activation marker IBA-1 as well as the production of ROS, NO, and proinflammatory cytokines (TNF-alpha and IL-1 beta). In primary microglial cells, we also found that doxycycline inhibits LPS-induced p38 MAP kinase phosphorylation and NF-kB nuclear translocation. The present results indicate that the effect of doxycycline on LPS-induced microglial activation probably occurs via the modulation of p38 MAP kinase and NF-kB signaling pathways. These results support the idea that doxycycline may be useful in preventing or slowing the progression of PD and other neurodegenerative diseases that exhibit altered glia function. (AU)

• Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
• Beneficiário: Fernando de Queiroz Cunha
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 11/19670-0 - Mecanismos envolvidos na fisiopatologia da artrite reumatóide, dor e sepse
• Beneficiário: Fernando de Queiroz Cunha
• Modalidade de apoio: Auxílio à Pesquisa - Temático