Fig. 11

Mechanisms for the dust extract induction of inflammatory gene expression. The flow diagram shows how dust extracts induce inflammatory gene expression in lung epithelial cells. Exposure of cells to dust extracts increases intracellular reactive oxygen species (ROS) production and activates PAR-1 and PAR-2 to induce inflammatory gene expression. MMP-1 and MMP-13 that are induced by dust extract exposure can potentially activate PAR-1 to further modulate inflammatory gene expression. Protease inhibitors and antioxidants suppress protein kinase C (PKC) and NF-kB activation indicating that proteases and ROS are important players in signal transduction pathways for the induction of inflammatory gene expression. The role of PKC in the activation of PARs is yet to be studied. The inhibitors used to delineate the pathways are shown. α1-AT, alpha1-antitrypsin; SBTI, soybean trypsin inhibitor; NAC, n-acetylcysteine; DMTU, dimethylthiourea; CDDOIm, 1-(2-Cyano-3,12,28-trioxooleana-1,9(11)-dien-28-yl)-1H-imidazole. MMP, matrix metalloproteinase; PAR, protease activated receptor; PKC, protein kinase C, NF-kB, nuclear factor-kappaB