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

Author(s)

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]

Affiliation

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

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

• Document type: Journal article
• Source: NITRIC OXIDE-BIOLOGY AND CHEMISTRY; v. 89, p. 32-40, AUG 1 2019.
• Web of Science Citations: 2

Abstract

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)

• FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
• Grantee: Fernando de Queiroz Cunha
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 12/04132-6 - Role of D6 receptor in the inflammatory response development during sepsis
• Grantee: Fernanda Vargas e Silva Castanheira
• Support Opportunities: Scholarships in Brazil - Doctorate