Differences between males and females in the resolution of inflammation

Details

Supervisors

Al Houayek, Mireille

Faculty

Faculté de pharmacie et des sciences biomédicales

Degree label

Master [120] en sciences biomédicales, à finalité approfondie

Abstract

Many diseases have an inflammatory component. Current anti-inflammatory therapies are efficient in acute settings but find their limitations in chronic inflammation, with a lack or loss of effect coupled with side effects that affect the patients’ quality of life. Therefore, identifying the players that enable an active return to homeostasis and the repair of damaged tissues and adopting strategies aimed at inducing the resolution of inflammation has been proposed. It is in this context that my master thesis attempts to highlight the inter-sexual differences in the inflammatory response and in the mechanisms of its resolution. The first part of this master thesis is devoted to the study of changes in various inflammation parameters over time. To do so, we used the model of self-resolving peritonitis induced by zymosan A. We injected zymosan into the peritoneum of male and female mice, which were sacrificed at different times and a peritoneal lavage was performed. We obtained the classical kinetics of cell infiltration in the peritoneum reported for this model, with a peak of cell infiltration at 12 h post zymosan administration. Our results showed a higher infiltration of neutrophils in male mice compared to female mice between 12 and 16 h after zymosan administration. Cytokine production measured by ELISA was different between male and female mice at the various time points. Finally, neutrophil apoptosis and their efferocytosis by macrophages were also assessed with higher apoptosis in female mice at the 8 and 48 h timepoints. The second part of this master thesis is dedicated to in vitro cell activation. We incubated primary bone marrow-derived neutrophils and peritoneal macrophages with zymosan or Lipopolysaccharides to compare cell activation by these two compounds. Assessment of cytokine production by ELISA showed differences in cytokine production between cells from male and female mice. qRT-PCR was carried out to study the expression of various genes implicated in inflammation and resolution and showed different expression between cells from male and female mice.