269093 Regulatory role of miroRNAs upon blistering agent-mediated innate immunity in skin keratinocytes

Monday, October 29, 2012

Zachary B. Paras , Environmental Health Science, New York Medical College, School of Heath Sciences and practice, Valhalla, NY
Hong-Duck Kim , Environmental Health Science, New York Medical College, School of Heath Sciences and practice, Valhalla, NY
Michael P. Shakarjian , Environmental health Science, New York Medical College, School of Heath Sciences and practice,, Valhalla, NY
Jeffrey D. Laskin , Environmetal and Occupational Medicine, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ
Diane E. Heck , Environmental Health Science, New York Medical College, School of Heath Sciences and practice, Valhalla, NY
Skin is the body's predominant defense barrier against pathogens and environmental stimuli. Skin keratinocytes respond to toxic chemical exposure by secreting immunity factors that mobilize macrophages and T-cells. Upon the re-epithelialization process of chemically-damaged skin, cutaneous cell proliferation and inflammation cascades are activated. Increasing evidence has indicated that small, non-coding microRNAs (miR) regulate innate immunity, tissue repair, and inflammation. Currently, the signaling pathways that regulate the secretion of innate immunity soluble factors is unknown.

We used quantitative real-time PCR methodology (RT-QPCR) and a microRNA PCR array to amplify selected genes for the purpose of understanding the skin's protective response against nitrogen mustard (HN2)-mediated toxicity. The PAM212 mouse keratinocyte cell line was used as an in vitro skin model to investigate the interaction of innate immunity and skin inflammation. Cells were treated with 3ÁM of HN2 for 48h followed by RT-QPCR analysis. Interestingly, we found an overproduction of miR-183 and miR-21 in response to HN2 treatment in PAM212. These results correlate with an increase in pro-inflammatory signaling, IL-6 and TNF, and a decrease in the innate immunity receptors, TLR-2 and TLR-3. Furthermore, there was a decrease in anti-oxidant enzyme isotopes, GST-M1 and GST-T1, and the selected chemokine, CCL-27, post-HN2 exposure.

We conclude that HN2 may dysregulate cellular defense systems comprised of innate immunity receptors, antioxidant enzymes, T-cells, and chemokines. Furthermore, miR-21 and miR-183 may regulate these defense mechanisms in keratinocytes. Finally, TLR-2 and TLR-3 may serve as biomarkers to assess the extent of cellular damage and the success of therapeutic countermeasures under a clinical and public health surveillance paradigm.

Learning Areas:
Basic medical science applied in public health
Environmental health sciences
Other professions or practice related to public health
Public health biology
Public health or related research

Learning Objectives:
Assess environmental chemical toxicant exposures on skin. Define mustard-mediated cellular defense mechanisms in immune response. Evaluate role of microRNA regulation of cellular defense mechanism. Identify role of innate immunity receptors as a biomarker to assess public health surveillance therapy.

Keywords: Environmental Exposures, Toxicants

Presenting author's disclosure statement:

Qualified on the content I am responsible for because: I am the principal investigator of the abstract. I am currently an MPH student at New York Medical College. I am a research associate of the Department of Environmental Health Sciences. I have presented a poster at the 2011 APHA conference (environmental section), in addition, have abstract/presenter experience from the Public Health Association of New York City (PHANYC) and Society of Toxicology.
Any relevant financial relationships? No

I agree to comply with the American Public Health Association Conflict of Interest and Commercial Support Guidelines, and to disclose to the participants any off-label or experimental uses of a commercial product or service discussed in my presentation.