The β2-adrenergic receptor agonist terbutaline upregulates T helper-17 cells in a protein kinase A-dependent manner.

Autor: Carvajal Gonczi CM; Department of Biology, PERFORM Centre, Concordia University, Montreal, Quebec, Canada., Hajiaghayi M; Department of Biology, PERFORM Centre, Concordia University, Montreal, Quebec, Canada., Gholizadeh F; Department of Biology, PERFORM Centre, Concordia University, Montreal, Quebec, Canada., Xavier Soares MA; Department of Biology, PERFORM Centre, Concordia University, Montreal, Quebec, Canada., Touma F; Department of Biology, PERFORM Centre, Concordia University, Montreal, Quebec, Canada., Lopez Naranjo C; Department of Biology, PERFORM Centre, Concordia University, Montreal, Quebec, Canada., Rios AJ; Department of Biology, PERFORM Centre, Concordia University, Montreal, Quebec, Canada., Pozzebon C; Department of Psychology, PERFORM Centre, Concordia University, Montreal, Quebec, Canada., Daigneault T; Department of Biology, PERFORM Centre, Concordia University, Montreal, Quebec, Canada., Burchell-Reyes K; Department of Chemistry and Biochemistry, PERFORM Centre, Concordia University, Montreal, Quebec, Canada., Darlington PJ; Department of Biology, PERFORM Centre, Concordia University, Montreal, Quebec, Canada; Department of Psychology, PERFORM Centre, Concordia University, Montreal, Quebec, Canada; Department of Health, Kinesiology & Applied Physiology, PERFORM Centre, Montreal, Quebec, Canada. Electronic address: peter.darlington@concordia.ca.
Jazyk: angličtina
Zdroj: Human immunology [Hum Immunol] 2023 Oct; Vol. 84 (10), pp. 515-524. Date of Electronic Publication: 2023 Jul 10.
DOI: 10.1016/j.humimm.2023.06.007
Abstrakt: Background: T helper 17 (Th17) cells produce IL-17A cytokine and can exacerbate autoimmune diseases and asthma. The β2 adrenergic receptor is a g protein-coupled receptor that induces cAMP second messenger pathways. We tested the hypothesis that terbutaline, a β2-adrenergic receptor-specific agonist, promotes IL-17 secretion by memory Th17 cells in a cAMP and PKA-dependent manner.
Methods: Venous peripheral blood mononuclear cells (PBMC) from healthy human participants were activated with anti-CD3 and anti-CD28 antibodies. Secreted IL-17A was measured by enzyme linked immunosorbent assay, intracellular IL-17A, and RORγ were measured using flow cytometry, and RORC by qPCR. Memory CD3 + CD4 + CD45RA - CD45RO + T cells were obtained by immunomagnetic negative selection and activated with tri-antibody complex CD3/CD28/CD2. Secreted IL-17A, intracellular IL-17A, RORC were measured, and phosphorylated-serine133-CREB was measured by western blotting memory Th cells.
Results: Terbutaline increased IL-17A (p < 0.001), IL-17A + cells (p < 0.05), and RORC in activated PBMC and memory Th cells. The PKA inhibitors H89 (p < 0.001) and Rp-cAMP (p < 0.01) abrogated the effects of terbutaline on IL-17A secretion in PBMC and memory T cells. Rolipram increased IL-17A (p < 0.01) to a similar extent as terbutaline. P-Ser133-CREB was increased by terbutaline (p < 0.05) in memory T cells.
Conclusion: Terbutaline augments memory Th17 cells in lymphocytes from healthy participants. This could exacerbate autoimmune diseases or asthma, in cases where Th17 cells are considered to be pro-inflammatory.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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