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Exposure to Hst1 or LL-37 resulted in a dose-dependent increase in CCL20 from both skin and gingiva keratinocytes, with LL-37 being more potent than Hst1.
Skin-derived keratinocyte-fibroblast cocultures (ratio 25:75) exposed to 50 [micro]M Hst1 showed a 12-fold increase in CCL20 secretion, and gingiva cocultures showed a >3-fold increase.
Since synergism occurred with regard to CCL20 secretion in response to Hst1 and LL-37, we next performed cross-over experiments in order to identify the mechanism.
These results indicate that Hst1 and LL-37 increase CCL20 secretion in an IL-1[alpha]-, TNF-[alpha]-, CCL27-, CCL28-, and IL18-independent manner.
Hst1 was unable to increase IL-1[alpha] and CCL27 secretion by skin or gingiva keratinocytes (Figure 3(a)).
Similar to our findings with CCL20, neither Hst1 nor LL-37 was able to increase IL-6, CXCL1, CXCL8, or CCL2 secretion by fibroblasts derived from skin or gingiva (Figure 3(b)).
In contrast, Hst1 exposure resulted in slight trends for increased secretion of the inflammatory mediators with only significance occurring for CCL2 secretion.
In this study, we have shown that peptides which are present in human saliva, Hst1 and LL-37, can stimulate host cells (skin and gingiva fibroblasts and keratinocytes) to secrete known antimicrobial and inflammatory mediators (CCL20, IL-1[alpha], IL-6, CCL2, CCL27, CXCL1, and CXCL8) [23-25].
We found that Hst1 and LL-37 stimulated keratinocytes to secrete CCL20.
With regard to Hst1, we would like to emphasize that no cytotoxicity was observed even at concentrations as high as 50 [micro] M (MTT assay and visual inspection with a microscope).
Taken together, our results show that Hst1 and LL-37 can stimulate host cells to secrete antimicrobial CCL20 via an, as yet, unknown mechanism.
Caption: Figure 1: Cell viability after exposure to Hst1 and LL-37.
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- HST Airborne Support Equipment
- HST Anomaly Report
- HST Digital Imaging System
- HST Instrument Servicing
- HST Integration and Test Anomaly Report
- HST Orbital Systems Test
- HST REV
- HST rotation