O-11 ENHANCEMENT OF F4/80+CD11B-CD206+ KUPFFER CELLS IN LIVER TISSUE: EFFECT OF MARESIN-1 AS HEPATOPROTECTIVE AGENT

Introduction and Objectives

Chronic liver diseases (CLD) are a major global health burden and are the 11th leading cause of death and the 15th cause of morbidity worldwide. CLD could be associated with steatosis and fibrosis and progress to cirrhosis, with the concomitant liver failure. Currently, there is no approved treatment and it is only recommended to eliminate the causative agent or give palliative treatments. The immune response, particularly hepatic macrophages (Kupffer cells), play a fundamental role in the development of liver disease. It is known that well-differentiated populations coexist in the liver, including: F4/80+CD11b- (sessile) and F4/80+CD11b+ (migrated from bone marrow). These populations could be modified their phenotype from M1 (inflammatory) to M2 (anti-inflammatory), which is of pharmacological interest. We aimed to study the administration of Maresin-1, a derivative of omega-3 fatty acids, promote a restorative state by an increase in the CD206+CD86-CD11c- i.e. M2 Kupffer cell population.

Materials and Methods

male C57bl/c mice were subjected to liver fibrosis by i.p diethylnitrosamine (DEN) 50 mg/kg twice a week and treated with MaR1 (4ng/g) for 9 weeks. The liver macrophages were isolated: real-time qPCR flow and cytometry were made. In addition, MaR1 was administered to healthy mice to observe the role MaR1 on hepatic macrophage populations.

Results

The administration of MaR1 modifies the Kupffer cells populations, generating an increase in the subpopulations of M2 F4/80+CD11b-CD206+ and F4/80intCD11b+CD206+, with a decrease in the CD86+CD11c+, both in the fibrosis as in healthy mice. This was accompanied by an increase in IL-10 cytokines and a fall in TNF-a values.

Conclusions

Taken together, these results indicate that Mar1 switches the Kupffer cells towards an anti-inflammatory, restorative and resolving state, acting as a hepatoprotective agent.