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Sigma receptor 1 activation attenuates release of inflammatory cytokines MIP1?, MIP2, MIP3?, and IL12 (p40/p70) by retinal Muller glial cells.

ABSTRACT: The high-affinity sigma receptor 1 (?R1) ligand (+)-pentazocine ((+)-PTZ) affords profound retinal neuroprotection in vitro and in vivo by a yet-unknown mechanism. A common feature of retinal disease is Müller cell reactive gliosis, which includes cytokine release. Here, we investigated whether lipopolysaccharide (LPS) stimulates cytokine release by primary mouse Müller cells and whether (+)-PTZ alters release. Using a highly sensitive inflammatory antibody array we observed significant release of macrophage inflammatory proteins (MIP1?, MIP2, MIP3?) and interleukin-12 (IL12 (p40/p70)) in LPS-treated cells compared to controls, and a significant decrease in secretion upon (+)-PTZ treatment. Müller cells from ?R1 knockout mice demonstrated increased MIP1?, MIP2, MIP3? and IL12 (p40/p70) secretion when exposed to LPS compared to LPS-stimulated WT cells. We investigated whether cytokine secretion was accompanied by cytosolic-to-nuclear NF?B translocation and whether endothelial cell adhesion/migration was altered by released cytokines. Cells exposed to LPS demonstrated increased NF?B nuclear location, which was reduced significantly in (+)-PTZ-treated cells. Media conditioned by LPS-stimulated-Müller cells induced leukocyte-endothelial cell adhesion and endothelial cell migration, which was attenuated by (+)-PTZ treatment. The findings suggest that release of certain inflammatory cytokines by Müller cells can be attenuated by ?R1 ligands providing insights into the retinal neuroprotective role of this receptor.

SUBMITTER: Shanmugam A

PROVIDER: S-EPMC4451448 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Sigma receptor 1 activation attenuates release of inflammatory cytokines MIP1γ, MIP2, MIP3α, and IL12 (p40/p70) by retinal Müller glial cells.

Shanmugam Arul A Wang Jing J Markand Shanu S Perry Richard L RL Tawfik Amany A Zorrilla Eric E Ganapathy Vadivel V Smith Sylvia B SB

Journal of neurochemistry 20150129 5

The high-affinity sigma receptor 1 (σR1) ligand (+)-pentazocine ((+)-PTZ) affords profound retinal neuroprotection in vitro and in vivo by a yet-unknown mechanism. A common feature of retinal disease is Müller cell reactive gliosis, which includes cytokine release. Here, we investigated whether lipopolysaccharide (LPS) stimulates cytokine release by primary mouse Müller cells and whether (+)-PTZ alters release. Using a highly sensitive inflammatory antibody array we observed significant release ...[more]

PMID: 25439327

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Dataset Information

Sigma receptor 1 activation attenuates release of inflammatory cytokines MIP1?, MIP2, MIP3?, and IL12 (p40/p70) by retinal Muller glial cells.

Publications

Sigma receptor 1 activation attenuates release of inflammatory cytokines MIP1γ, MIP2, MIP3α, and IL12 (p40/p70) by retinal Müller glial cells.

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