capable of causing orexacerbating lung diseases by directly affecting signaling pathways involved incell migration, and remodeling of the airway. Therefore arsenic ingestion mayalter wound response and specifically, MMP-9/TIMP-1 ratios in the lung.Following scrapewounds of monolayer cultures, Arsenic(30–290 ppb) was capable of inhibiting the reformation of the epithelialmonolayer. An increase in activity and expression ofMMP-9 without increases of TIMP-1 protein expression was also observedalong with this alteration in wound repair.
Furthermore, an improvement inepithelial cell wound repair response was seen after inhibition of MMP-9 eventhough the cells were exposed to 290 ppb arsenic. To conclude, arsenic iscapable of altering the airway epithelial barrier as arsenic induced increase in MMP-9/TIMP-1ratio in lung epithelial cells can restrict proper wound repair.MMP-9expression has been associated with airway epithelial woundrepair in primary cultured cells and in vivo. Moreover, neutralizing MMP-9using antibodies inhibited migration of HRECs indicating that MMP-9 wasimportant in cell migration during respiratory wound repair. Moreover, MMP-9expression directly coincided with the speed of migration in HBECs. Therefore,MMP-9 is normally upregulated in cells near the wound edge and in the presenceof arsenic, dysregulated wound repair was observed due to MMP-9 overexpressionin airway epithelial cells. In the fibroblast model,alterations in focal adhesion kinases, without a significant effect on actincytoskeleton rearrangements were observed at about 200 ppb arsenite.
Thisresulted in altered cell migration independent of MMP-9. There are alsocontrasting reports showing that 750 ppb arsenic of unknown form alters actincytoskeleton and can lead to superoxide production and limit cell migration inan endothelial cell line. In contrast with observationsthat arsenite can inhibit migration,there are also reports that show arsenic(37.5–375 ppb) in the form of arsenic trioxide (As2O3) can reduce carcinogeniccell invasiveness in carcinogenic cell lines in part by downregulating MMP-9(15, 46, 53) ArsenicInduces Cell Transformation at low concentrations and Apoptosis at HigherConcentrationsLower concentrations ofarsenite (0.5–25 ?M) exposure was capable of producing anchorage-independentcolonies of JB6 Cl 41 cells. But a higher concentration of arsenic (200 ?M)induce apoptosis, thereby preventing the cells from undergoing transformation.
DifferentialActivation of Erks and JNKs by Arsenite