| Texto completo | |
| Autor(es): |
da Rocha, Gustavo Henrique Oliveira
[1]
;
de Paula-Silva, Marina
[1]
;
Broering, Milena Fronza
[1]
;
Scharf, Pablo Rhasan dos Santos
[1]
;
Matsuyama, Larissa Satiko Alcantara Sekimoto
[1]
;
Maria-Engler, Silvya Stuchi
[1]
;
Farsky, Sandra Helena Poliselli
[1]
Número total de Autores: 7
|
| Afiliação do(s) autor(es): | [1] Univ Sao Paulo, Fac Pharmaceut Sci, Dept Clin & Toxicol Anal, Sao Paulo - Brazil
Número total de Afiliações: 1
|
| Tipo de documento: | Artigo Científico |
| Fonte: | FRONTIERS IN PHARMACOLOGY; v. 11, DEC 21 2020. |
| Citações Web of Science: | 0 |
| Resumo | |
Ulcerative colitis and Crohn's disease are chronic inflammatory bowel diseases (IBDs) which burden health systems worldwide; available pharmacological therapies are limited and cost-intensive. Use of peroxisome proliferator activated-receptor gamma (PPAR gamma) ligands for IBD treatment, while promising, lacks solid evidences to ensure its efficacy. Annexin A1 (AnxA1), a glucocorticoid-modulated anti-inflammatory protein, plays a key role on IBD control and is a potential biomarker of IBD progression. We here investigated whether effects of pioglitazone, a PPAR gamma ligand, rely on AnxA1 actions to modulate IBD inflammation. Experimental colitis was evoked by 2% dextran sodium sulfate (DSS) in AnxA1 knockout (AnxA1(-/-)) or wild type (WT) C57BL/6 mice. Clinical and histological parameters were more severe for AnxA(-/-) than WT mice, and 10 mg/kg pioglitazone treatment attenuated disease parameters in WT mice only. AnxA1 expression was increased in tissue sections of diseased WT mice, correlating positively with presence of CD68(+) macrophages. Metalloproteinase-9 (MMP-9) and inactive 33 kDa AnxA1 levels were increased in the colon of diseased WT mice, which were reduced by pioglitazone treatment. Cytokine secretion, reactive oxygen species generation and MMP-9 expression caused by lipopolysaccharide (LPS) treatment in AnxA1-expressing RAW 264.7 macrophages were reduced by pioglitazone treatment, effects not detected in AnxA1 knockdown macrophages. LPS-mediated increase of AnxA1 cleaving in RAW 264.7 macrophages was also attenuated by pioglitazone treatment. Finally, pioglitazone treatment increased extracellular signal-regulated kinase (ERK) phosphorylation in AnxA1-expressing RAW 264.7 macrophages, but not in AnxA1-knockdown macrophages. Thus, our data highlight AnxA1 as a crucial factor for the therapeutic actions of pioglitazone on IBDs. (AU) | |
| Processo FAPESP: | 16/19682-2 - Mecanismos de ação da anexina A1 na doença intestinal inflamatória tratada com infliximabe |
| Beneficiário: | Marina de Paula Silva |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado |
| Processo FAPESP: | 17/05430-4 - Efeitos da interação entre anexina A1 e PPAR gama sobre o desenvolvimento de colite experimental |
| Beneficiário: | Gustavo Henrique Oliveira da Rocha |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado |
| Processo FAPESP: | 14/07328-4 - Identificação de vias endógenas para o controle da inflamação |
| Beneficiário: | Sandra Helena Poliselli Farsky |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |