Effects of Contact Allergens on Innate Immune Cells

• Author / Creator

  Green, Christopher D

• The characteristics which cause a particular chemical to be a contact irritant, a contact allergen, or have no apparent interaction with our skin are not well understood, but undoubtedly complex. We propose that contact allergens, which are those chemicals that have the capacity to induce sensitization and the subsequent development of allergic contact dermatitis, possess two fundamental, but independent, properties: (1) the ability to create a non-self T-cell epitope by reacting with self-proteins within the skin, and (2) the ability to simultaneously activate the innate immune system to provide the necessary co-stimulatory signals required for sensitization. The latter property is the focus of this thesis. We first developed and characterized a proinflammatory cytokine-based assay, using the human monocytic cell line THP-1 as a model innate immune cell. Release of TNF-α, IL-8, IL-6 and IL-1β were measured following exposure of THP-1 cells to an array of contact allergens. We found that contact allergens, but not contact irritants, elicited robust innate immune cell activation. We then utilized parental and human Toll-like receptor 4 (hTLR4) transfected HEK293 cells to screen selected contact allergens to determine if they, like Nickel, also signal through hTLR4. We independently found that two Nickel-related contact allergens, Cobalt and Palladium, also elicit immune responses through hTLR4, while the eleven other contact allergens tested do not. Lastly, we attempted to find, or create, a THP-1 based reporter assay which would be suitable for high-throughput investigations to discover novel signaling pathways used by other contact allergens. While these efforts ultimately proved unsuccessful, direct measurement of inflammatory cytokines from THP-1 cells should prove to be a useful tool for the purposes of siRNA screens or related approaches.

• Subjects / Keywords

  • Contact Hypersensitivity
  • Allergic Contact Dermatitis
  • Contact Allergen

• Graduation date

  Fall 2014

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/R3N67G

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.