HMGB1 induced inflammatory effect is blocked by CRISPLD2 via MiR155 in hepatic fibrogenesis

• CRISPLD2 can be up-regulated by HMGB1 stimulation in a time dependent manner.
• Up-regulation of CRISPLD2 is TLR4 dependent via miR155 and knockdown the expression of CRISPLD2 can enhance HMGB1-induced inflammation.
• CRISPLD2 severs as an endogenous anti-inflammatory protein which can curtail inflammation in a number of inflammation related processes.

A number of studies have showed that High mobility group box-1 (HMGB1), which played key role in inflammation activation by triggering the toll like receptor 4 (TLR4) signaling axis in hepatic fibrogenesis, may share similar inflammation stimulating mechanism with LPS. Herein, we introduced a recently established anti-LPS protein cysteine-rich secretory protein LCCL domain containing 2 (CRISPLD2) to investigate endogenous protection mechanism of HMGB1 induced inflammatory response. Our results shows that stromal cells and monocytes showed an evaluated pattern for CRISPLD2 expression after HMGB1 treatment, which was dependent on the integrity of TLR4 function. Pro-inflammatory Cytokines levels were significantly elevated after CRISPLD2 silencing despite the HMGB1 status. Soluble CRISPLD2 administration relieve the HMGB1 dependent pro-inflammatory cytokines release. Interestingly, we found that miRNA 155 play a key role in the process. Our data suggest that CRISPLD2 may have a unique anti-HMGB1 effect via miRNA and play an important role in immune balance.