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Interleukin 1 expression is inducible by nerve growth factor in PC12 pheochromocytoma cells
K Alheim1, C Andersson, S Tingsborg
1Department of Biochemistry, Arrheniuslaboratory, Stockholm University, Sweden.
Insights
This study shows that nerve growth factor (NGF) can significantly increase the expression of interleukin-1 alpha (IL-1 alpha) in PC12 cells. This finding highlights a potential regulatory loop between NGF and IL-1 alpha in neural tissues.
Area of Science:
- Neuroscience
- Molecular Biology
- Immunology
Background:
- Interleukin-1 alpha (IL-1 alpha) is a cytokine with known roles in inflammation and cell proliferation.
- PC12 pheochromocytoma cells are a widely used model system in neuroscience research, particularly for studying neuronal differentiation and growth factors.
Purpose of the Study:
- To investigate the expression of IL-1 alpha in rat PC12 pheochromocytoma cells.
- To determine if nerve growth factor (NGF) influences IL-1 alpha expression in these cells.
Main Methods:
- Immunohistochemistry using specific antibodies.
- Enzyme-linked immunosorbent assay (ELISA).
- Cell conversion bioassay.
- Reverse transcription polymerase chain reaction (RT-PCR) to detect IL-1 alpha mRNA.
Main Results:
- Constitutive expression of IL-1 alpha and its mRNA was detected in PC12 cells.
- Nerve growth factor (7S NGF) significantly induced IL-1 alpha expression at both mRNA and protein levels.
- Maximum induction of IL-1 alpha reached 600% after 3 days of NGF treatment (0.75 µg/ml).
Conclusions:
- PC12 cells express IL-1 alpha, and this expression is regulated by NGF.
- The NGF-induced IL-1 alpha may play a role in glial proliferation and potentially forms a feedback loop with NGF, as IL-1 alpha can induce NGF expression.
- This suggests a complex interplay between neurotrophic factors and cytokines in neural tissue regulation and repair.
Abstract:
Expression of the cytokine interleukin 1 alpha (IL-1 alpha) was demonstrated in the rat PC12 pheochromocytoma cell line by (i) immunohistochemistry using rabbit polyclonal antisera raised against the recombinant murine IL-1 alpha, (ii) an ELISA, and (iii) a specific cell conversion bioassay based on the use of LBRM33-1A5 cells. IL-1 alpha mRNA was demonstrated in the PC12 cells, by PCR amplification. Constitutive expression of IL-1 alpha in PC12 cells was demonstrated in all experiments, although the cellular levels of IL-1 alpha-like immunoreactivity varied. The expression of IL-1 alpha, as studied at the mRNA level, was inducible by mouse nerve growth factor (7S NGF), and the gene product level was inducible in a dose- and time-dependent fashion by 7S NGF. The maximum induction corresponds to a 600% increase in IL-1 alpha-like immunoreactivity above the expression level found in noninduced cells and occurred after a 3-day incubation of the cells with NGF at 0.75 micrograms/ml of culture medium. The significance of the ability of NGF to induce IL-1 expression lies in the fact that IL-1 itself also acts as a growth factor that promotes glial proliferation and, even more importantly, IL-1 itself induces the expression of NGF at peripheral nerve injury [Lindholm, D., Heumann, R., Meyer, M. & Thoenen, H. (1987) Nature (London) 330, 658-659].
