The Role of Nik-related kinase in Regulating IL-10 Expression
(2022) MOBM02 20221Degree Projects in Molecular Biology
- Popular Abstract
- Nik-related kinase: A New IL-10 Regulator
Our body is constantly exposed to microscopic organisms called microbes. Some of these organisms are harmless while others are able to cause infection and damage. Thus, our body has defense mechanisms that include the immune system. Macrophages are cells that belong to the immune system and have key roles in defense against infection, wound healing, and regulation of general tissue function. During infection, as a part of protective measure, macrophages sense and respond to conserved components of microbes. One such component is the bacterial lipopolysaccharide (LPS), which stimulates macrophages to produce and secrete multiple signaling molecules to communicate with other cells. These signaling... (More) - Nik-related kinase: A New IL-10 Regulator
Our body is constantly exposed to microscopic organisms called microbes. Some of these organisms are harmless while others are able to cause infection and damage. Thus, our body has defense mechanisms that include the immune system. Macrophages are cells that belong to the immune system and have key roles in defense against infection, wound healing, and regulation of general tissue function. During infection, as a part of protective measure, macrophages sense and respond to conserved components of microbes. One such component is the bacterial lipopolysaccharide (LPS), which stimulates macrophages to produce and secrete multiple signaling molecules to communicate with other cells. These signaling molecules are called cytokines, and different cytokines send different signals to surrounding cells. When macrophages sense e.g. LPS, they use distinct but overlapping pathways inside the cell to generate each cytokine. These signaling pathways are highly complex and involve many different proteins. Recently, our lab has identified the protein Nik-related kinase (Nrk) as potentially having an important role in the pathways that lead to production of a cytokine called interleukin-10 (IL-10).
The main function of IL-10 is to dampen or inhibit inflammation. Other cytokines, such as IL-6 and TNF have the opposite function – to start or increase inflammation. In this study, we aimed to investigate whether Nrk is only important for making IL-10, or if it also affects the generation of IL-6 and TNF. Using an experimental system of pure macrophages that we stimulated with LPS, we found that macrophages that have been modified so they no longer have the Nrk protein still generate the same amount of IL-6 and TNF as non-modified macrophages, but they generated much less IL-10. From this result, we can conclude that Nrk is involved in production of IL-10, but not IL-6 or TNF in macrophages. This is critical in limiting the excessive inflammation during infection by regulating the production of pro-inflammatory cytokines.
We have mentioned previously that several signaling pathways regulate the production of cytokines including IL-10. Some of these pathways are mediated through major kinases, such as Jnk, p38, and Erk1/2. As it has been previously suggested that Nrk may activate Jnk, but not Erk1/2 or p38. Here we set off to study if Nrk is required to activate Jnk but not Erk or p38 signaling pathways in macrophages. Cells were stimulated with LPS and were analyzed for kinases activation. We didn’t find activation differences in any of the major kinases in both modified and non-modified macrophages after LPS stimulation. This indicates that Nrk is not required to activate Erk1/2, p38, and Jnk. These observations suggest that Nrk might be involved in other pathways or activates other kinases that regulate the IL-10 production. In conclusion, a better understanding of how Nrk contributes specifically to the anti-inflammatory IL-10 production may be fundamental in developing effective therapeutic strategies for several inflammatory diseases.
Master’s Degree Project in Molecular Biology and Microbiology, 30 credits.
Department of Biology, Lund University.
Advisor: Jenny J Persson
Dept of Experimental Medical Science, Section for Immunology
BMC D14, Lund University Sweden (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/9082085
- author
- Nsaif, Mohammad
- supervisor
- organization
- course
- MOBM02 20221
- year
- 2022
- type
- H2 - Master's Degree (Two Years)
- subject
- language
- English
- id
- 9082085
- date added to LUP
- 2022-05-31 10:53:28
- date last changed
- 2022-05-31 10:53:28
@misc{9082085, author = {{Nsaif, Mohammad}}, language = {{eng}}, note = {{Student Paper}}, title = {{The Role of Nik-related kinase in Regulating IL-10 Expression}}, year = {{2022}}, }