Figure 6.

Heme-induced inflammatory and proliferative lung diseases are mediated through MKK3/P38 axis. Free heme-activated MKK3 triggered the p38 pathway, leading to the initiation of inflammatory and proliferative signaling cascades ERK1/2/STAT3/Akt. Moreover, heme treatment-induced barrier dysfunction decreases the expression of tight junction proteins (ZO-1) and facilitates inflammatory cell infiltration. However, the absence of MKK3 attenuated heme-induced inflammatory cell infiltration, cytokine storm, and pulmonary vascular remodeling.