Wound healing phenotype of oral mucosal wounds in Interleukin-12/-23 deficient mice.

Marie Anne Teresa J. Matias (2011). Wound healing phenotype of oral mucosal wounds in Interleukin-12/-23 deficient mice. PhD Thesis, School of Dentistry, The University of Queensland.

       
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Author Marie Anne Teresa J. Matias
Thesis Title Wound healing phenotype of oral mucosal wounds in Interleukin-12/-23 deficient mice.
School, Centre or Institute School of Dentistry
Institution The University of Queensland
Publication date 2011-06
Thesis type PhD Thesis
Supervisor Professor Laurence Walsh
Professor Mike Waters
Professor Saso Ivanovski
Total pages 327
Total colour pages 26 pages in main thesis and 115 in APPENDIX section
Total black and white pages 186
Subjects 11 Medical and Health Sciences
Abstract/Summary The desire to improve soft tissue healing after surgery, trauma or from disease has been an ongoing objective. Deficiencies in our understanding of the precise cellular and molecular mechanisms in wound healing are obstacles to generating treatment outcomes that are predictable, rapid and regenerative. The orchestrated events of wound healing are conducted by finely tuned activation and inactivation of regulatory molecules involving interactions by resident cells, extracellular matrix and the immune system. The inter-relationship of inflammation, host immunity and the progress of wound healing have been supported by a number of animal models, such as wound healing studies in cytokine knockout mice. These studies have produced significant findings, improving our knowledge of the molecular mechanisms in the wound healing cascade, as well as solidifying the link between inflammation, immunity and tissue repair/regeneration. This thesis investigates the potential role of the p40 molecule (IL-12/IL-23p40) which is shared by two inflammatory cytokines, interleukin-12 (IL-12) and interleukin-23 (IL-23) in soft tissue healing. These pro-inflammatory cytokines may affect wound healing by influencing the nature of the inflammatory response to wounding. In addition, IL-12 and IL-23 can influence angiogenesis, which is an essential component of wound healing. This work highlights the impact of the inflammatory response initiated after wounding, the linkage between host immune responses and wound healing, and provides insights into potential therapeutic targets that may be used to improve healing of soft tissue wounds. This study used an oral mucosal wound healing model based on excisional tongue biopsies. This is the first study to demonstrate that a deficiency of IL-12 and IL-23 in mice is associated with an accelerated healing phenotype. The accelerated rate of re-epithelialization of oral mucosal wounds observed in the knockout mice indicates that an endogenous absence of IL-12, IL-23 and p40 favourably influenced wound healing. The results described in this thesis suggest that specific profiles for chemokines and cytokines seen in the knockout mice parallel the key events of early recruitment of phagocytes, enhanced epithelialization, and early establishment of angiogenesis. Furthermore, the data presented infer that MMP-9 and its effects on angiogenesis may be one of the key linkages that directly associates deficiency of IL-12 with angiogenesis. Taken together, the expression profiles for chemokines, cytokines and matrix enzymes seen in the IL-12/IL-23p40-/- mice synchronises with the key events which facilitate an early wound healing response. This includes the early establishment of an inflammatory response and subsequent early establishment of angiogenesis which contribute to the favourable healing phenotype observed. The work presented in this thesis identified specific areas for further investigation that may provide opportunities to alter wound healing events that will result in accelerated and regenerative healing.
Keyword interleukin-12
INTERLEUKIN-23
p40 molecule
wound healing
Angiogenesis
Matrix Metalloproteinase
Additional Notes In the main text: page numbers as printed on the text include colour pages for: page 41, 47, 53, 55, 57, 58, 79, 80, 104, 105, 106, 108 to 114, 133, 135, 136, 138, 140, 143, 145 and 154. In appendix section (no page number on printed text) page number relates to page number allocated by pdf file page number... 197 to 299; 312 to 321 and 323 to 327

 
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Created: Wed, 26 Oct 2011, 08:52:46 EST by Dr Marie Matias on behalf of Library - Information Access Service