Down‐regulation of β‐adrenergic receptors induced by mitogen activation of intracellular signaling events in lymphocytes

doi:10.1016/0014-5793(95)00366-h

Cited by 36 publications

(4 citation statements)

References 32 publications

(33 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Finally, the inability of TERB to reduce IL-2 production in spleen and DLN cells from AA rats is consistent with recent findings from our lab that β 2 -ARs are uncoupled from cAMP (18). Others have reported that IL-2 decreases β-AR density, removing a negative control over cellular proliferation (45). Similarly, in certain cell populations, IL-1β can impair β 2 -AR coupling with adenylate cyclase (46, 47).…”

Section: Discussionmentioning

confidence: 99%

Targeting Î±- and Î²-Adrenergic Receptors Differentially Shifts Th1, Th2, and Inflammatory Cytokine Profiles in Immune Organs to Attenuate Adjuvant Arthritis

et al. 2014

View full text Add to dashboard Cite

The sympathetic nervous system (SNS) regulates host defense responses and restores homeostasis. SNS-immune regulation is altered in rheumatoid arthritis (RA) and rodent models of RA, characterized by nerve remodeling in immune organs and defective adrenergic receptor (AR) signaling to immune cell targets. The SNS typically promotes or suppresses inflammation via α- and β2-AR activation, respectively, and indirectly drives humoral immunity by blocking Th1 cytokine secretion. Here, we investigate how β2-AR stimulation and/or α-AR blockade at disease onset affects disease pathology and cytokine profiles in relevant immune organs from male Lewis rats with adjuvant-induced arthritis (AA). Rats challenged to induce AA were treated with terbutaline (TERB), a β2-AR agonist (600 μg/kg/day) and/or phentolamine (PHEN), an α-AR antagonist (5.0 mg/kg/day) or vehicle from disease onset through severe disease. We report that in spleen, mesenteric (MLN) and draining lymph node (DLN) cells, TERB reduces proliferation, an effect independent of IL-2. TERB also fails to shift T helper (Th) cytokines from a Th1 to Th2 profile in spleen and MLN (no effect on IFN-γ) and DLN (greater IFN-γ) cells. In splenocytes, TERB, PHEN, and co-treatment (PT) promotes an anti-inflammatory profile (greater IL-10) and lowers TNF-α (PT only). In DLN cells, drug treatments do not affect inflammatory profiles, except PT, which raised IL-10. In MLN cells, TERB or PHEN lowers MLN cell secretion of TNF-α or IL-10, respectively. Collectively, our findings indicate disrupted β2-AR, but not α-AR signaling in AA. Aberrant β2-AR signaling consequently derails the sympathetic regulation of lymphocyte expansion, Th cell differentiation, and inflammation in the spleen, DLNs and MLs that is required for immune system homeostasis. Importantly, this study provides potential mechanisms through which reestablished balance between α- and β2-AR function in the immune system ameliorates inflammation and joint destruction in AA.

show abstract

Section: Discussionmentioning

confidence: 99%

Targeting Î±- and Î²-Adrenergic Receptors Differentially Shifts Th1, Th2, and Inflammatory Cytokine Profiles in Immune Organs to Attenuate Adjuvant Arthritis

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Of the 11 PDE families characterized to date, isoforms belonging to the relatively strong-affinity (147) cAMP-binding families of PDE1 (145, 148), PDE3 (145, 149), PDE4 (145, 149), PDE7 (145, 149–151), PDE8 (145, 151, 152), and PDE11 (145) have been observed within T cells, with most cAMP hydrolysis carried out by PDE3 and PDE4 isoforms (148, 149, 153). Of note, cAMP levels in T cells can also be augmented by additional factors in the TME including prostaglandin E 2 (PGE 2 ) (154), norepinephrine (155), histamine (156), the neuropeptides VIP and PACAP (157, 158), and low pH (159). Additional phenomena contributing toward cAMP build-up within effector T cells include TCR triggering (160, 161) as well as direct cAMP transfer by tumor cells (162) or Tregs (163) via gap junctions.…”

Section: Adenosine-induced Intracellular Camp Accumulation Impairs T mentioning

confidence: 99%

Targeting Adenosine in Cancer Immunotherapy to Enhance T-Cell Function

et al. 2019

View full text Add to dashboard Cite

T cells play a critical role in cancer control, but a range of potent immunosuppressive mechanisms can be upregulated in the tumor microenvironment (TME) to abrogate their activity. While various immunotherapies (IMTs) aiming at re-invigorating the T-cell-mediated anti-tumor response, such as immune checkpoint blockade (ICB), and the adoptive cell transfer (ACT) of natural or gene-engineered ex vivo expanded tumor-specific T cells, have led to unprecedented clinical responses, only a small proportion of cancer patients benefit from these treatments. Important research efforts are thus underway to identify biomarkers of response, as well as to develop personalized combinatorial approaches that can target other inhibitory mechanisms at play in the TME. In recent years, adenosinergic signaling has emerged as a powerful immuno-metabolic checkpoint in tumors. Like several other barriers in the TME, such as the PD-1/PDL-1 axis, CTLA-4, and indoleamine 2,3-dioxygenase (IDO-1), adenosine plays important physiologic roles, but has been co-opted by tumors to promote their growth and impair immunity. Several agents counteracting the adenosine axis have been developed, and pre-clinical studies have demonstrated important anti-tumor activity, alone and in combination with other IMTs including ICB and ACT. Here we review the regulation of adenosine levels and mechanisms by which it promotes tumor growth and broadly suppresses protective immunity, with extra focus on the attenuation of T cell function. Finally, we present an overview of promising pre-clinical and clinical approaches being explored for blocking the adenosine axis for enhanced control of solid tumors.

show abstract

“…Beta-2 adrenoceptores are the most commonly found amongst adrenergic receptors in almost all cells of the immune system [79, 80], a noteworthy exception being Th2 clones [81]. Decreased density and signaling via these receptors is usually seen at the peak of T-cell activation, which may be relevant to unleashing these cells to their full potential [82, 83]. Additionally, agonist binding to beta-2 adrenoceptors expressed by B cells, natural killer (NK), and macrophages lead to changes in their activity [84–86].…”

Section: The Autonomic Nervous System (Ans) and Immune Responsesmentioning

confidence: 99%

Neural Pathways in Allergic Inflammation

et al. 2010

View full text Add to dashboard Cite

Allergy is on the rise worldwide. Asthma, food allergy, dermatitis, and systemic anaphylaxis are amongst the most common allergic diseases. The association between allergy and altered behavior patterns has long been recognized. The molecular and cellular pathways in the bidirectional interactions of nervous and immune systems are now starting to be elucidated. In this paper, we outline the consequences of allergic diseases, especially food allergy and asthma, on behavior and neural activity and on the neural modulation of allergic responses.

show abstract

Down‐regulation of β‐adrenergic receptors induced by mitogen activation of intracellular signaling events in lymphocytes

Cited by 36 publications

References 32 publications

Targeting Î±- and Î²-Adrenergic Receptors Differentially Shifts Th1, Th2, and Inflammatory Cytokine Profiles in Immune Organs to Attenuate Adjuvant Arthritis

Targeting Î±- and Î²-Adrenergic Receptors Differentially Shifts Th1, Th2, and Inflammatory Cytokine Profiles in Immune Organs to Attenuate Adjuvant Arthritis

Targeting Adenosine in Cancer Immunotherapy to Enhance T-Cell Function

Neural Pathways in Allergic Inflammation

Contact Info

Product

Resources

About