Figure 9.

Proposed mechanism of action of AVR-48 in neonatal lungs. AVR-48 after binding to TLR4 triggers the TRIF pathway to activate the M2 macrophages via the alternate pathway to produce IL-10, which in turn negatively regulates TLR4 to downregulate the MyD88 pathway to decrease the synthesis of a myriad of pro-inflammatory cytokines and chemokines by suppressing the M1 macrophages that are produced via activation of the classical pathway during BPD. This combinatorial effect results in decreasing tissue injury and increasing tissue repair and healing by maintaining a balance between M2 and M1 macrophages toward a favorable outcome with overall improvement of the BPD cardiopulmonary phenotype.