We show that TLR4 is required for expression of IL-6 and SNAIL and that MCAM is required for VCAM1, and that while both receptors activate p-p38 and NF-κB, different signaling molecules are required to induce coactivating transcription factors, i.e., p-STAT1 for IL-6, p-JNK–mediated p-SMAD3 for SNAIL, and p-ERK–mediated ATF2 for VCAM1. The studies do reinforce the need for novel therapies in PAH such as the use of TLR4 inhibitors currently in clinical trial for autoimmune disease (46). Here, IL6 is linked to autoimmune disease.