Resumen:
Sex-dependent patterns in chronic immune-mediated cholangiopathies, like primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), remain poorly understood. Peroxisome proliferator-activated receptor alpha (PPAR-& alpha;), expressed in immune cells, plays a key role in innate defence. In this study, the relationship between PPAR-& alpha; expression in peripheral blood mononuclear cells (PBMCs), serum androgen levels, IFN & gamma; production, and sex-dependent tendencies during the development of PBC and PSC was investigated. We confirmed that normal cholangiocytes respond to PPAR-& alpha; and inhibit the lipopolysaccharide-induced expression of IL-6, IL-1b, and TNF & alpha;. Compared with PSC patients, PPAR-& alpha; was downregulated, while IFN & gamma; was upregulated, in the PBMCs of PBC patients. When the analysis was conducted on females only, there was no difference in PPAR-& alpha;, but IFN & gamma; was elevated in females with PBC compared with those with PSC. Serum testosterone concentrations in females with PBC were below the normal range (regardless of age) and correlated positively with PPAR-& alpha; and negatively with IFN & gamma;. While PPAR-& alpha; has been reported to be a target of miR-155 and miR-21, no correlations with these microRNAs were observed in the PBMCs. However, a positive correlation between miR-21 and IFN & gamma; was observed. Our results showed suppressed PPAR-& alpha; expression accompanied by reduced testosterone levels in women with PBC, which should elicit interest in the role of testosterone in PBC development.
