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Neutrophil-Derived COX-2 has a Key Role during Inflammatory Hyperalgesia

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Carvalho, Nathalia Santos ; Paes Lemes, Julia Borges ; Pagliusi Jr, Marco ; dos Santos Machado, Ana Carolina ; Malange, Kaue Franco ; Pral, Lais Passariello ; Fachi, Jose Luis ; Nishijima, Catarine Massucato ; dos Santos, Gilson Goncalves ; Tambeli, Claudia Herrera ; Sartori, Cesar Renato ; Ramirez Vinolo, Marco Aurelio ; Parada, Carlos Amilcar
Total Authors: 13
Document type: Journal article
Source: Inflammation; v. 45, n. 6, p. 14-pg., 2022-07-15.
Abstract

Inflammation is a vital process for the injured tissue restoration and one of its hallmarks is inflammatory hyperalgesia. The cyclooxygenase (COX) pathway is strongly related to the inflammatory and painful process. Usually, the COX-1 isoform is described as homeostatic, while COX-2 is characterized as inducible in inflammatory conditions. Although it is well known that neutrophil cells are the first to arrive at the inflamed site and the major source of COX-2 is still unknown, the specific role of neutrophil-derived COX-2 in the pain process is. Thus, in the present study, we demonstrate for the first time that neutrophil-derived COX-2 plays a key role in peripheral inflammatory hyperalgesia. Conditional knockout mice for COX-2 in neutrophils (COX-2( fl/fl: Mrp8cre +/-)) exhibited higher pain sensitivity after carrageenan (CG) injection and long-lasting IL-1 beta-induced hyperalgesia compared with the control group (COX-2( fl/fl)). Also, CG-induced inflammation in COX-2( fl/fl: Mrp8cre +/-) mice showed COX-1 overexpression, and increased neutrophil migration and pro-inflammatory cytokines (e.g., IL-1 beta and CXCL1). These findings revealed that neutrophil COX-2 has an important role in the regulation of inflammatory hyperalgesia. (AU)

FAPESP's process: 17/07162-7 - Contribution of COX-2 expression of neutrophils in the inflammatory process and in hyperalgesia during experimental Rheumatoid Arthritis induced by collagen in mice
Grantee:Nathalia Santos Carvalho
Support Opportunities: Scholarships in Brazil - Doctorate