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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Lipopolysaccharide reduces urethral smooth muscle contractility via cyclooxygenase activation

Texto completo
Autor(es):
Calmasini, Fabiano B. [1] ; Alexandre, Eduardo C. [1] ; Oliveira, Mariana G. [1] ; Silva, Fabio H. [2] ; Soares, Antonio G. [3] ; Costa, Soraia K. P. [3] ; Antunes, Edson [1]
Número total de Autores: 7
Afiliação do(s) autor(es):
[1] Univ Estadual Campinas, Dept Pharmacol, Fac Med Sci, BR-13084971 Campinas, SP - Brazil
[2] Sao Francisco Univ USF, Lab Multidisciplinary Res, Braganca Paulista, SP - Brazil
[3] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Sao Paulo - Brazil
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY; v. 77, n. 4, p. 557-564, NOV 2021.
Citações Web of Science: 0
Resumo

Lipopolysaccharide (LPS) is a component of gram-negative bacteria wall that elicits inflammatory response in the host through the toll-like receptor 4 (TLR4) activation. In the lower urinary tract (LUT), bacteria-derived LPS has been associated with lower urinary tract symptoms (LUTS); however, little is known about the effects of LPS in the urethral smooth muscle (USM). In the present study, we evaluated the functional and molecular effects of LPS in mouse USM in vitro, focusing on the LPS-induced TLR4-signaling pathway. Male C57BL6/JUnib and TLR4 knockout mice (TLR4 KO) were used. The USM contraction was performed in the presence of LPS (62.5-500 mu g/mL), indomethacin (10 mu M), L-NAME (100 mu M), and TAK 242 (1 mu M). The RT-PCR assay for the IL-1 beta, NF-kB, and COX-2 genes was also evaluated in the presence of LPS (125 mu g/mL) and caspase 1 inhibitor (20 mu M). Our results showed that LPS reduces mouse USM contraction elicited by phenylephrine and vasopressin. This LPS-induced urethral inhibitory effect was not reversed by the TLR4 inhibition or its absence in the TLR4 KO mice. Conversely, indomethacin (but not L-NAME) reversed the LPS-induced USM hypocontractility. Molecular protocols indicated upregulation of IL-1 beta, NF-k beta, and COX-2 mRNA upon LPS incubation, which were blunted by caspase 1 inhibition. Our data showed that LPS reduced mouse USM contraction independently of TLR4 activation, involving caspase 1 and IL1 beta, NF-kB, and COX-2 gene overexpression. Therefore, this alternative pathway might be a valuable target to reduce the LPS-induced urethral dysfunction under infection and inflammatory conditions. (AU)

Processo FAPESP: 17/15175-1 - Modulação da guanilato ciclase solúvel e dos níveis intracelulares de nucleotídeos cíclicos em órgãos do trato urinário inferior e próstata
Beneficiário:Edson Antunes
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 16/01178-6 - Estudo da hiperreatividade prostática em camundongos obesos resistentes à insulina: Papel dos receptores TLR4.
Beneficiário:Fabiano Beraldi Calmasini
Linha de fomento: Bolsas no Brasil - Pós-Doutorado