Isoproterenol-induced beta-2 adrenergic receptor activation negatively regulates interleukin-2 signaling.
Biochem J
; 475(18): 2907-2923, 2018 09 18.
Article
en En
| MEDLINE
| ID: mdl-30120106
ABSTRACT
Regulation of intracellular signaling pathways in lymphocytes is critical for cell homeostasis and immune response. Interleukin-2 (IL-2), a key regulator of lymphocytes, signals following receptor-ligand engagement and subsequent recruitment and activation of effector proteins including JAKs and STATs. Lymphocytes can also be regulated by the central nervous system through the ß2 adrenergic receptor (ß2AR) pathway which can affect cell trafficking, proliferation, differentiation, and cytokine production. The cross-talk between these two signaling pathways represents an important mechanism that has yet to be fully elucidated. The present study provides evidence for communication between the IL-2 receptor (IL-2R) and ß2AR. Treatment of human lymphoid cell lines with the ß2AR agonist isoproterenol (ISO) alone increased cAMP levels and mediated a stimulatory response by activating AKT and ERK to promote cell viability. Interestingly, ISO activation of ß2AR also induced threonine phosphorylation of the IL-2Rß. In contrast, ISO treatment prior to IL-2 stimulation produced an inhibitory signal that disrupted IL-2 induced activation of the JAK/STAT, MEK/ERK, and PI3K pathways by inhibiting the formation of the IL-2R beta-gamma chain complex, and subsequently cell proliferation. Moreover, γc-family cytokines-mediated STAT5 activation was also inhibited by ISO. These results suggest a molecular mechanism by which ß2AR signaling can both stimulate and suppress lymphocyte responses and thus explain how certain therapeutic agents, such as vasodilators, may impact immune responsiveness.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Linfocitos
/
Interleucina-2
/
Receptores Adrenérgicos beta 2
/
Sistema de Señalización de MAP Quinasas
/
Agonistas de Receptores Adrenérgicos beta 2
/
Isoproterenol
Límite:
Humans
Idioma:
En
Revista:
Biochem J
Año:
2018
Tipo del documento:
Article
País de afiliación:
Estados Unidos