037 – Role of beta2-adrenergic receptors (Beta2AR) in the LPS-induced secretion of cytokines by astrocyte

Electronic Poster | Session 2

037 – Role of beta2-adrenergic receptors (Beta2AR) in the LPS-induced secretion of cytokines by astrocyte

Paulo Santos (1) – Juliana Maricato (2) – Alexandre Basso (2)
Biomedical Science Institute, University of São Paulo, São Paulo, Brazil (1) – Federal University of São Paulo, Department of Microbiology, Immunology and Parasitology, São Paulo, Brazil (2)


Multiple Sclerosis (MS) is considered to be an autoimmune disease in which T lymphocytes react against antigens of an important component of the Central Nervous System (CNS): the myelin sheath. Experimental autoimmune encephalomyelitis (EAE) is one of the best animal models to study MS. Astrocytes play an important role in EAE pathogenesis by producing cytokines and chemokines via NF-B-dependent pathways. These molecules modulate the activity and the migration of inflammatory cells, and the permeability of the blood-brain barrier. The Sympathetic Nervous System (SNS) can modulate EAE development by interfering with the generation of the adaptive immune response. However, whether and how the SNS is able to influence EAE through adrenergic receptors expressed by astrocytes is not known. We have shown that signaling via beta2-adrenergic receptors (beta2AR) reduces the expression of proinflammatory cytokines in dendritic cells and macrophages, an effect that was associated with the inhibition of the NF-kappaB pathway. In this study, we demonstrated that astrocytes derived from mixed cortical cultures produce IL-6, TNF-alpha and CCL2 after being stimulated with lipopolysaccharide (LPS) in a time-dependent manner. Furthermore, the expression of CCL-2 and TNF-alpha are downregulated when astrocytes are previously treated with Fenoterol and Norepinephrine, agonists of the beta2AR. In addition to that, the beta2AR-mediated inhibition of LPS-induced release of TNF-alpha and CCL2 relies on the beta2AR canonical signaling pathway. Hence, protein kinase A (PKA) inhibition, by the previous treatment of astrocytes with H89, prevented the beta2AR-mediated decrease in LPS-induced production of TNF-alpha and CCL2, but not the translocation of NF-kappaB to the nucleus. Thus, when stimulated in vitro with LPS, astrocytes are able to produce cytokines and chemokines and this production is modulated by beta2AR activation in a canonical manner. This work is developed at the Laboratory of Neuroimmunology, at Universidade Federal de São Paulo (UNIFESP).
Key words: Astrocyte; Sympatethic Nervous System; Beta2AR; EAE; MS.