Scavenger receptor class A ligands induce secretion of IL1β and exert a modulatory effect on the inflammatory activation of astrocytes in culture

Abstract

Class-A Scavenger receptor (SR-A) is expressed by microglia, and we show here that it is also expressed by astrocytes, where it participates on their inflammatory activation. Astrocytes play a key role on the inflammatory response of the central nervous system, secreting several soluble mediators like cytokines and radical species. Exposure to SRs ligands activated MAPKs and NF-κB signaling and increase production of IL1β and nitric oxide (NO). IL1β classically an inflammatory cytokine surprisingly did not increase but inhibited LPS+IFNγ-induced NO production by astrocytes. Our results suggest that SRs expressed by astrocytes participate in the modulation of inflammatory activation.

Innate Immunity and Neuroinflammation

“…SRs are expressed on macrophages, dendritic cells, microglia, and endothelial cells [111, 112]. Recently, SR expression on astrocytes has been reported [166]. The family of SRs include class A (macrophage receptors, MARCO), class B (CD36, SR-BI), CD68 and endothelial or LOX-1, CD163, and receptor for advanced glycation end products (RAGE) [167, 168].…”

“…However, deficiency of SR-A in AD mouse models was not found to impact amyloid plaque deposition or clearance [181]. In vitro studies have shown that astrocytes express SR-A and thus play a role in neuroinflammation [166]. Class B SR Type I (SR-BI) has been shown to be produced in vivo in AD brains [182] with increased expression being observed in cerebellum and cortex [183].…”

Role of Scavenger Receptors in Glia-Mediated Neuroinflammatory Response Associated with Alzheimer’s Disease

“…Furthermore, our group was the first to describe the expression of SR-A by astrocytes, showing that exposure to SR-A ligands activated MAPKs and NF κ B signaling pathways and increased the production of IL-1 β and NO by astrocytes [115]. …”

Scavenger Receptor-A (CD204): A Two-Edged Sword in Health and Disease

“…In vitro studies indicate that SR-AIII may serve as a dominant negative regulator of SR-A I/II function. 38 SR-A is preferentially expressed on macrophages; 1,2,8,41–43 however, SR-A has been described in vascular smooth muscle cells, 44–46 endothelial cells (EC), 47–51 human lung epithelial cells, 28 microglia, 52,53 astrocytes, 54 and murine embryonic fibroblasts. 29 Bickel and Freeman showed that the gene for SR-A could be induced in cultured smooth muscle cells by stimulation with phorbol myristate acetate; however, they did not detect SR-A mRNA in rabbit venous EC or bovine aortic EC.…”

“…44 In contrast, Hashizume and Mihara showed induction of SR-A mRNA and protein in cultured human aortic EC after stimulation with tumor necrosis factor alpha (TNFα) or interleukin 6. 51 Although SR-A is named the scavenger receptor and is predominately found on macrophages, the recent observations that an SR-A message is expressed in endothelial cells, 51 lung epithelial cells, 28 microglia, 52,53 astrocytes, 54 and primary murine fibroblasts, 29 broadens the scope of the pathophysiologic importance of SR-A.…”