Targeting nitric oxide as a key modulator of sepsis, arthritis and pain

Autor(es)

Spiller, Fernando ^[1] ; Formiga, Rodrigo Oliveira ^[1] ; da Silva Coimbra, Jonathan Fernandes ^[1] ; Alves-Filho, Jose Carlos ^[2] ; Cunha, Thiago Mattar ^[2] ; Cunha, Fernando Queiroz ^[2]

Afiliação do(s) autor(es)

^[1] Fed Univ Santa Catarina UFSC, Dept Pharmacol, Florianopolis, SC - Brazil

^[2] Univ Sao Paulo, Ribeiro Preto Med Sch, Dept Pharmacol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: NITRIC OXIDE-BIOLOGY AND CHEMISTRY; v. 89, p. 32-40, AUG 1 2019.
• Citações Web of Science: 2

Resumo

Nitric oxide (NO) is produced by enzymatic activity of neuronal (nNOS), endothelial (eNOS), and inducible nitric oxide synthase (iNOS) and modulates a broad spectrum of physiological and pathophysiological conditions. The iNOS isoform is positively regulated at transcriptional level and produces high levels of NO in response to inflammatory mediators and/or to pattern recognition receptor signaling, such as Toll-like receptors. In this review, we compiled the main contributions of our group for understanding of the role of NO in sepsis and arthritis outcome and the peripheral contributions of NO to inflammatory pain development. Although neutrophil iNOS-derived NO is necessary for bacterial killing, systemic production of high levels of NO impairs neutrophil migration to infections through inhibiting neutrophil adhesion on microcirculation and their locomotion. Moreover, neutrophil-derived NO contributes to multiple organ dysfunction in sepsis. In arthritis, NO is chief for bacterial clearance in staphylococcal-induced arthritis; however, it contributes to articular damage and bone mass degradation. NO produced in inflammatory sites also downmodulates pain. The mechanism involved in analgesic effect and inhibition of neutrophil migration is dependent on the activation of the classical sGC/cGMP/PKG pathway. Despite the increasing number of studies performed after the identification of NO as an endothelium-derived relaxing factor, the underlying mechanisms of NO in inflammatory diseases remain unclear. (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: 12/04132-6 - Papel do receptor D6 no desenvolvimento da resposta inflamatória durante a sepse
• Beneficiário: Fernanda Vargas e Silva Castanheira
• Modalidade de apoio: Bolsas no Brasil - Doutorado