| dc.creator | Rivera Ramirez, Evasomary | |
| dc.creator | Jiménez Vélez, Braulio (Consejero) | |
| dc.date | 2015-01-08T19:36:38Z | |
| dc.date | 2015-01-08T19:36:38Z | |
| dc.date | 2015-01-08T19:36:38Z | |
| dc.date.accessioned | 2017-03-17T16:54:41Z | |
| dc.date.available | 2017-03-17T16:54:41Z | |
| dc.identifier | http://hdl.handle.net/10586 /528 | |
| dc.identifier.uri | http://repositorioslatinoamericanos.uchile.cl/handle/2250/647644 | |
| dc.description | Epidemiological, clinical, in vivo and in vitro studies have shown consistent
associations between particulate matter (PM) exposure and the induction of
pro-inflammatory responses. Post transcriptional control mechanisms are essential in the
regulation of pro-inflammatory mediators such as IL-6 and IL-8; however the role of PM
exposure in the post transcriptional control of IL-6 and IL-8 has not been evaluated.
Therefore the hypothesis of this study is that exposure to PM2.5 promotes the
stabilization of IL-6 and IL-8 mRNAs by the AU-rich elements (AREs) mediated
pathway. This hypothesis was addressed through the following specific aims: 1)
Evaluate the effects of PM2.5 in the induction of IL-6 and IL-8; 2). Evaluate the role of
PM2.5 in the mRNA stability of IL-6 and IL-8; and 3). Determine if PM2.5 promotes the
activation of the AU-rich binding proteins HuR and AUF-1. Organic extracts derived
from PM2.5 collected in Guaynabo and Fajardo were used to test the hypothesis. In
addition a standard reference material for diesel exhaust particles (DEP) was used. In
vitro studies with a human bronchial epithelial cell line showed that our extracts were
able to induce the production of IL-6 and IL-8 with significant increases in mRNA
steady-state levels as early as 15 min of exposure. The mRNA half-lives were
significantly increased in exposed cells indicating that the mRNA were being stabilized.
To confirm if the mRNA stabilization was due to post-transcriptional control
mechanisms, nuclear run-ons assays were conducted to measure the transcription rates
of the IL-6 and IL-8 genes. Only the Guaynabo extract and DEP induce de novo
synthesis of IL-8 at 15 min, indicating that transcriptional mechanisms were also at play.
The involvement of the HuR and AUF-1 in the stabilization of the mRNAs was explored by measuring their levels in the cytoplasm. While AUF-1 was not detected, a
cytoplasmic enrichment of HuR was observed in cells exposed to the Guaynabo extract.
Overall, this study demonstrated for the first time that PM exerts an effect in the
transcriptional and post transcriptional regulation of IL-6 and IL-8, providing evidence of
molecular mechanisms involved in the adverse health effects observed with PM. | |
| dc.language | en | |
| dc.subject | Interleukin-6 | |
| dc.subject | Interleukin-8 | |
| dc.subject | Post-transcriptional control mechanism | |
| dc.subject | mRNA stability | |
| dc.subject | particulate matter exposure | |
| dc.subject | pro-inflammatory | |
| dc.subject | toxicology | |
| dc.subject | molecular mechanisms | |
| dc.title | Effects of Atmospheric Particulate Matter on the Post-Transcriptional Control of the Pro-inflamatory Mediators Interleukin-6 and Interleukin-8 | |
| dc.type | Tesis | |
