An altered response to Resistin in monocytes and liver macrophages contributes to inflammation in adult patients with Non-alcoholic Fatty Liver Disease

BAZ PLACIDA; PONCINO DANIEL; ALEJANDRA C. CHERÑAVSKY; CECILIA GARCIA; COLOMBATO LUIS; GONDOLESI GABRIEL; BENAVIDEZ JAVIER; DESCALZI VALERIA

CABA

Congreso; Reunión anuel de Sociedades de Biociencias 2020; 2020

Comité de Sociedades Argentinas de Biociencias

Background: Resistin (Res), a cytokine produced by monocytes (Mo) and macrophages, is highly expressed in blood and liver of patients with nonalcoholic fatty liver disease (NAFLD). Res binds to adenylate cyclase-associated protein 1 (CAP1). CAP1 expression and Res-mediated effects are unexplored in NAFLD. Aims: to evaluate CAP1 expression and Res-mediated modulation of CD69, IL-6 and phagocytosis in Mo and liver macrophages (LM) from NAFLD. Methods: we included blood and liver samples from controls (Co, n=40) and NAFLD patients (n=30). CAP1 expression was studied by flow cytometry (FC). To evaluate CD69 expression, peripheral blood mononuclear cells (PBMC) were stimulated with PMA (10 ng/ml) +/- Res (10 ng/ml) for 24 h. IL-6 production was induced using LPS (20 ng/ml) +/- Res for 19 h. Phagocytosis in presence or absence of Res was evaluated by FC using fluorescent beads. Paired t test or Friedman test were used to evaluate effects within experimental groups, and unpaired t test or Mann-Whitney test for comparisons between groups. Results: CAP1 expression was higher in Mo and LM from NAFLD than Co (p=0.002 and 0.022). Res partially prevented the PMA-induced increase in the frequency of Mo and LM expressing CD69 in Co (p= 0.005 and 0.012). Res partially prevented LPS-induced IL-6 production in Mo from Co (p=0.025). PMA-induced Mo CD69+ frequency and LPS-induced IL-6 production were higher in NAFLD than Co (p=0.016 and 0.001). However, Res-induced modulation of CD69 and IL-6 in NAFLD was not observed. Res induced an increase in phagocytosis percentage in Mo from Co (p=0.008) but not from NAFLD.Conclusion: Res modulates activation, cytokine production, and phagocytosis in monocytes from controls but not from NAFLD patients. Although CAP1 expression was elevated, Res-induced response is diminished in monocytes and liver macrophages from NAFLD patients. An altered response to resistin in monocytes and liver macrophages contributes to inflammation in NAFLD.