Following alterations in focal adhesion kinases, without a significant

Following scrapewounds of monolayer cultures, Arsenic (30–290 ppb) was capable of inhibiting the reformation of the epithelial monolayer. An increase in activity and expression ofMMP-9 without increases of TIMP-1 protein expression was also observed along with this alteration in wound repair. Furthermore, an improvement in epithelial cell wound repair response was seen after inhibition of MMP-9 even though the cells were exposed to 290 ppb arsenic. To conclude, arsenic is capable of altering the airway epithelial barrier as arsenic induced increase in MMP-9/TIMP-1 ratio in lung epithelial cells can restrict proper wound repair.

MMP-9 expression has been associated with airway epithelial wound repair in primary cultured cells and in vivo. Moreover, neutralizing MMP-9 using antibodies inhibited migration of HRECs indicating that MMP-9 was important in cell migration during respiratory wound repair. Moreover, MMP-9 expression directly coincided with the speed of migration in HBECs. Therefore, MMP-9 is normally upregulated in cells near the wound edge and in the presence of arsenic, dysregulated wound repair was observed due to MMP-9 overexpression in airway epithelial cells.

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In the fibroblast model, alterations in focal adhesion kinases, without a significant effect on actin cytoskeleton rearrangements were observed at about 200 ppb arsenite. This resulted in altered cell migration independent of MMP-9. There are also contrasting reports showing that 750 ppb arsenic of unknown form alters actin cytoskeleton and can lead to superoxide production and limit cell migration in an endothelial cell line. In contrast with observations that arsenite can inhibit migration,there are also reports that show arsenic (37.5–375 ppb) in the form of arsenic trioxide (As2O3) can reduce carcinogenic cell invasiveness in carcinogenic cell lines in part by downregulating MMP-9 (15, 46, 53)