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Published on: September 7, 2018
Expression of preproenkephalin mRNA and production and secretion of enkephalins by human thymocytes
1Department of Pediatric Immunology, Room KC 03.068.0, Wilhelmina Children Hospital, University Medical Center Utrecht, PO BOX 85090, 3508 AB Utrecht, The Netherlands. a.kavelaars@wkz.azu.nl
Abstract:
Human thymocytes were tested for the capacity to express the preproenkephalin (PPE) gene and for production of the end product metenkephalin (MENK). It is shown here for the first time that the cytokines IL-2, IL-4, IL-6, and TGF-beta are capable of inducing PPE mRNA expression. Moreover, a culture of thymocytes with the cytokines results in intracellular expression of MENK as determined by immunohistochemistry. Thymocytes do not secrete detectable amounts of MENK, however, but only the larger MENK-containing peptides or proteins. Cytokines IL-1 beta and IL-10 increase the expression of PPE mRNA in 50% of the thymuses tested, whereas IFN-gamma does not induce changes in PPE mRNA expression.
Insights
Certain cytokines, including IL-2, IL-4, IL-6, and TGF-beta, can induce preproenkephalin (PPE) gene expression in human thymocytes, leading to met-enkephalin (MENK) production. Thymocytes express MENK intracellularly but secrete larger precursor peptides.
Area of Science:
- Immunology
- Neuroendocrinology
- Molecular Biology
Background:
- Human thymocytes are crucial for T-cell development.
- The role of thymocytes in opioid peptide production is not well understood.
- Preproenkephalin (PPE) gene expression and met-enkephalin (MENK) production in thymocytes warrant further investigation.
Purpose of the Study:
- To investigate the capacity of human thymocytes to express the PPE gene.
- To determine the effect of various cytokines on PPE gene expression and MENK production in thymocytes.
- To characterize the form of MENK produced and secreted by thymocytes.
Main Methods:
- Human thymocytes were cultured and treated with specific cytokines.
- PPE mRNA expression was assessed using molecular techniques.
- Intracellular MENK expression was determined via immunohistochemistry.
- Secreted products were analyzed to identify MENK-containing peptides.
Main Results:
- Interleukins (IL-2, IL-4, IL-6) and transforming growth factor-beta (TGF-beta) significantly induced PPE mRNA expression in thymocytes.
- Immunohistochemistry confirmed intracellular MENK expression following cytokine treatment.
- Thymocytes did not secrete detectable mature MENK but released larger MENK-containing precursor peptides.
- IL-1 beta and IL-10 increased PPE mRNA in 50% of samples; IFN-gamma had no effect.
Conclusions:
- Specific cytokines can induce PPE gene expression and intracellular MENK production in human thymocytes.
- Thymocytes process and store MENK intracellularly, releasing precursor forms rather than mature met-enkephalin.
- These findings reveal a novel immunomodulatory role for cytokines in thymocyte opioid peptide expression.
