Objective: To detect T cell immunoglobulin and mucin domain-containing molecule 3(Tim-3) expression on peripheral blood monocyts (PBMs) and explore its effect on inflammatory cytokines production of PBMs in patients with chronic hepatitis B (CHB).
Methods: The expression of Tim-3 protein and mRNA on PBM subsets was respectively determined using flow cytometry and real-time quantitative RT-PCR (qRT-PCR) in CHB patients at different phases. After PBMs were stimulated with both recombinant human galectin-9 and lipopolysaccharide (LPS) in active CHB patients, the supernatants were collected to measure the levels of proinflammatory factors including TNF-α, IL-1β and IL-6 by ELISA.
Results: Compared with healthy controls and CHB patients at immune active (IA) phase, the expression of Tim-3 was significantly up-regulated in PBMs of CHB patients at immune tolerance (IT) phase (P<0.01). The level of Tim-3 expression on both CD14(+);CD16-; and CD14(+);CD16(+); monocyte subsets of CHB patients at IT phase was significantly higher than that of the CHB patients at IA phase and of healthy controls (P<0.05). qRT-PCR further demonstrated that the level of Tim-3 mRNA on monocytes of CHB patients at IA phase was also higher than that of healthy controls (P=0.040). There was a positive correlation between the expression of Tim-3 on CD14(+); monocytes and serum ALT level in IA CHB patients (r=0.362, P=0.028). The levels of proinflammatory factors in supernatants, such as TNF-α, IL-1β and IL-6 increased significantly in monocytes stimulated by LPS and galectin-9, compared with ones by LPS alone.
Conclusion: Tim-3 expression, which is up-regulated on PBMs of CHB patients, is negatively correlated to the level of ALT in sera of IA CHB patients, and Tim-3/galectin-9 pathway might promote proinflammatory factors production of monocytes stimulated with LPS.