UNASSIGNED: The high-affinity sigma receptor 1 (  R1) ligand @entity12586 ((+)- @entity17202 ) affords profound retinal neuroprotection in vitro and in vivo by a yet-unknown mechanism. A common feature of @entity989 is M  ller cell reactive gliosis, which includes cytokine release. Here, we investigated whether lipopolysaccharide (LPS) stimulates cytokine release by primary @entity19 M  ller cells and whether (+)- @entity17202 alters release. Using a highly sensitive inflammatory antibody array we observed significant release of macrophage inflammatory proteins (MIP1y, @entity9701 , @entity13948 ) and interleukin-12 (IL12 ( @entity12782 / @entity11000 )) in LPS-treated cells compared to controls, and a significant decrease in secretion upon (+)- @entity17202 treatment. M  ller cells from   R1 knockout @entity19 demonstrated increased MIP1y, @entity9701 , @entity13948 and IL12 ( @entity12782 / @entity11000 ) secretion when exposed to LPS compared to LPS-stimulated WT cells. We investigated whether cytokine secretion was accompanied by cytosolic-to-nuclear NFkB translocation and whether endothelial cell adhesion/migration was altered by released cytokines. Cells exposed to LPS demonstrated increased NFkB nuclear location, which was reduced significantly in (+)- @entity17202 -treated cells. Media conditioned by LPS-stimulated-M  ller cells induced leukocyte-endothelial cell adhesion and endothelial cell migration, which was attenuated by @entity17202 treatment. The findings suggest that release of certain inflammatory cytokines by M  ller cells can be attenuated by   R1 ligands providing insights into the retinal neuroprotective role of this receptor. A common feature of @entity989 is M  ller cell reactive gliosis, which includes cytokine release. To understand how sigma receptor 1 (  R1) mediates neuroprotection, we examined the effects of a high-affinity   R1 ligand, @entity12586 , on LPS-stimulated cytokine release in primary @entity19 retinal M  ller glial cells. Under basal conditions, cytokine release was minimal. LPS stimulation markedly increased secretion of the cytokines MIP1y, @entity9701 , @entity13948 , IL12 ( @entity12782 / @entity11000 ), which was accompanied by a significant translocation of NFkB from cytoplasm to the nucleus. LPS-treatment in the presence of @entity12586 markedly decreased cytokine release accompanied by a significant decrease in NFkB localized to the nucleus. IL, interleukin; MIP, macrophage inflammatory proteins.

Sigma receptor 1 activation attenuates release of inflammatory cytokines MIP1y, XXXX , @entity13948 , and IL12 ( @entity12782 / @entity11000 ) by retinal M  ller glial cells.

@entity17202 :: ('D010433', 'Chemical') :: ['PTZ', '(+)-PTZ'] @entity12586 :: ('MESH:D010423', 'Chemical') :: ['(+)-pentazocine'] @entity12782 :: ('16160(Tax:10090)', 'Gene') :: ['p40'] @entity19 :: ('10090', 'Species') :: ['mice', 'mouse'] @entity9701 :: ('20310(Tax:10090)', 'Gene') :: ['MIP2'] @entity11000 :: ('16185(Tax:10090)', 'Gene') :: ['p70'] @entity989 :: ('MESH:D012164', 'Disease') :: ['retinal disease'] @entity13948 :: ('20297(Tax:10090)', 'Gene') :: ['MIP3a']
@entity9701 :: (20310(Tax:10090),Gene) :: ['MIP2']
