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You searched for +publisher:"University of Adelaide" +contributor:("Ferrante, Tony"). One record found.

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University of Adelaide

1. Melino, Michelle. The role of c-jun N-terminal kinase (JNK) in human T cell function.

Degree: 2009, University of Adelaide

T cells are involved in cellular pathways which enable the immune system to protect us against infection and cancer. However, the same mechanisms also allow T cells to generate chronic inflammatory conditions, including autoimmunity and allergy. Thus a concerted effort has been made to try to understand how the immune system functions in order to inhibit responses which may have harmful effects on tissues and organs. There is a continued search for new immunosuppressants which can only be accomplished through a better understanding of the pathways that regulate T cell function. This includes the intracellular signalling pathways which modulate T cell proliferation and cytokine production. While the Mitogen-Activated Protein Kinases (MAPK), extracellular signal-regulated protein kinases (ERK) and p38 have received attention, the role of the stress-activated protein kinases or c-jun N-terminal kinases (JNK) remains controversial. To overcome some of the limitations in studying the role of JNK, a new approach was taken in this thesis. The investigations used recently described peptides (TAT-JIP[subscript]153-163 and TAT-JIP[subscript]153-172) derived from the scaffold protein, JIP-1, which have previously been demonstrated to act as JNK pathway inhibitors. The research characterised the specificity of these inhibitors to enable the appropriate interpretation of data. Using these inhibitors, we were able to show that JNK regulated human T cell proliferation and cytokine production in T cell responses induced independently of TCR ligation (PHAPMA) or via the TCR (anti-CD3-anti-CD28 antibodies, Mixed Lymphocyte Reaction (MLR), Tetanus Toxoid and Der p 2). The data demonstrated that JNK primarily regulated the Th1 cytokine patterns (IFNγ, IL2 and LT) with minimal effect on Th2 cytokine production (IL4, IL10) in response to all stimulatory models. However, while the JNK signalling pathway promoted T cell proliferation and cytokine production in response to PHA-PMA, the pathway depressed these responses following stimulation with anti-CD3-anti-CD28 antibodies and Tetanus Toxoid. Thus activation of JNK with microbial pathogens such as Pseudomonas aeruginosa (PA), which non-specifically activate T cells, may promote lymphocyte proliferation and the release of Th1 cytokines, such as IFNγ. In contrast, JNK activation resulting from engagement of the T cell receptor (TCR) (i.e. Tetanus Toxoid), down-regulates Th1 cytokine production. Therefore, it is likely that the JNK signalling pathway may dampen the development of chronic inflammatory conditions resulting from infection with intracellular parasites and autoimmune diseases. In contrast to Tetanus Toxoid, responses to the recombinant house dust mite allergen, Dermatophagoides pteronyssinus (Der p 2) were promoted by JNK, leading to an increase in Th1 cytokine production. Thus the results suggest that the use of JNK inhibitors could exacerbate both inflammatory conditions (autoimmunity and allergy) and this may also apply to p38 but not the ERK signalling pathway. Advisors/Committee Members: Ferrante, Tony (advisor), McColl, Shaun Reuss (advisor), Hii, Charles Sung Teck (advisor), School of Molecular and Biomedical Science : Microbiology and Immunology (school).

Subjects/Keywords: T cells; cytokines; c-jun N-terminal kinase; mitogen-activated protein kinases

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APA (6th Edition):

Melino, M. (2009). The role of c-jun N-terminal kinase (JNK) in human T cell function. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/56209

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Melino, Michelle. “The role of c-jun N-terminal kinase (JNK) in human T cell function.” 2009. Thesis, University of Adelaide. Accessed April 19, 2019. http://hdl.handle.net/2440/56209.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Melino, Michelle. “The role of c-jun N-terminal kinase (JNK) in human T cell function.” 2009. Web. 19 Apr 2019.

Vancouver:

Melino M. The role of c-jun N-terminal kinase (JNK) in human T cell function. [Internet] [Thesis]. University of Adelaide; 2009. [cited 2019 Apr 19]. Available from: http://hdl.handle.net/2440/56209.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Melino M. The role of c-jun N-terminal kinase (JNK) in human T cell function. [Thesis]. University of Adelaide; 2009. Available from: http://hdl.handle.net/2440/56209

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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