Abstract
Previous studies implicated the anti-inflammatory potential of the adenosine 2B receptor (A2BAR). A2BAR activation is achieved through adenosine, but this is limited by its very short t(1/2). To further define alternative adenosine signaling, we examined the role of netrin-1 during acute inflammatory peritonitis. In this article, we report that animals with endogenous repression of netrin-1 (Ntn1(+/-)) demonstrated increased cell count, increased peritoneal cytokine concentration, and pronounced histological changes compared with controls in a model of zymosan A peritonitis. Exogenous netrin-1 significantly decreased i.p. inflammatory changes. This effect was not present in animals with deletion of A2BAR (A2BAR(-/-)). A2BAR(-/-) animals demonstrated no change in cell count, i.p. cytokine concentration, or histology in response to netrin-1 injection. These data strengthen the role of netrin-1 as an immunomodulatory protein exerting its function in dependence of the A2BAR and further define alternative adenosine receptor signaling.
Highlights
ObjectivesGiven the role of netrin-1 during hypoxic inflammation, we aimed to define its role during acute exudative inflammation and corroborate a possible role for the A2BAR
Netrin-1 is repressed during an acute inflammatory response We initially addressed the question of whether netrin-1 is expressed outside the CNS in intestinal organs to validate the model subsequently used; we found a robust expression of netrin-1 within several murine organs (Fig. 1A, 1B)
We aimed to identify whether netrin-1 expression is affected during an acute inflammatory process in the peritoneal cavity in vivo and found a significant reduction in netrin-1 in response to sterile peritonitis induced through zymosan A (ZyA) (Fig. 1C, 1D)
Summary
Given the role of netrin-1 during hypoxic inflammation, we aimed to define its role during acute exudative inflammation and corroborate a possible role for the A2BAR
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