Cytokine-induced SOCS expression is inhibited by cAMP analogue: Impact on regeneration in injured retina

Kevin Park, Ying Hu, Jillian Muhling, Margaret A. Pollett, Elizabeth J. Dallimore, Ann M. Turnley, Qi Cui, Alan R. Harvey

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Injured adult retinal ganglion cells (RGCs) regrow axons into peripheral nerve (PN) grafted onto cut optic nerve. Survival and regeneration of RGCs is increased by intraocular injections of ciliary neurotrophic factor (CNTF) and axonal regeneration is further enhanced by co-injection of a cyclic AMP analogue (CPT-cAMP). Based on these data, and because cytokine signaling is negatively regulated by suppressor of cytokine signaling (SOCS) proteins, we set out to determine whether CNTF injections increase retinal SOCS expression and whether any changes are attenuated by co-injection with CPT-cAMP. Using quantitative PCR we found increased SOCS1, SOCS2 and SOCS3 mRNA levels at various times after a single CNTF injection. Expression remained high for many days. SOCS protein levels were also increased. In situ hybridization revealed that RGCs express SOCS3 mRNA, and SOCS expression in cultured RGCs was increased by CNTF. Co-injection of CPT-cAMP reduced CNTF induced expression of SOCS1 and SOCS3 mRNA and decreased SOCS3 protein expression. CNTF injection also transiently increased retinal leukemia inhibitory factor (LIF) expression, an effect that was also moderated by CPT-cAMP. We propose that, along with known reparative effects of elevated cAMP on neurons, reducing SOCS upregulation may be an additional way in which cyclic nucleotides augment cytokine-induced regenerative responses in the injured CNS.

Original languageEnglish
Pages (from-to)313-324
Number of pages12
JournalMolecular and Cellular Neuroscience
Volume41
Issue number3
DOIs
StatePublished - Jun 22 2009
Externally publishedYes

Fingerprint

Ciliary Neurotrophic Factor
Retina
Regeneration
Retinal Ganglion Cells
Cytokines
Injections
Suppressor of Cytokine Signaling Proteins
Messenger RNA
Intraocular Injections
Leukemia Inhibitory Factor
Cyclic Nucleotides
Optic Nerve
Peripheral Nerves
Cyclic AMP
In Situ Hybridization
Axons
Cultured Cells
Up-Regulation
Neurons
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

Cytokine-induced SOCS expression is inhibited by cAMP analogue : Impact on regeneration in injured retina. / Park, Kevin; Hu, Ying; Muhling, Jillian; Pollett, Margaret A.; Dallimore, Elizabeth J.; Turnley, Ann M.; Cui, Qi; Harvey, Alan R.

In: Molecular and Cellular Neuroscience, Vol. 41, No. 3, 22.06.2009, p. 313-324.

Research output: Contribution to journalArticle

Park, Kevin ; Hu, Ying ; Muhling, Jillian ; Pollett, Margaret A. ; Dallimore, Elizabeth J. ; Turnley, Ann M. ; Cui, Qi ; Harvey, Alan R. / Cytokine-induced SOCS expression is inhibited by cAMP analogue : Impact on regeneration in injured retina. In: Molecular and Cellular Neuroscience. 2009 ; Vol. 41, No. 3. pp. 313-324.
@article{26873d59fba44a619dc4a4eea1e6bfe5,
title = "Cytokine-induced SOCS expression is inhibited by cAMP analogue: Impact on regeneration in injured retina",
abstract = "Injured adult retinal ganglion cells (RGCs) regrow axons into peripheral nerve (PN) grafted onto cut optic nerve. Survival and regeneration of RGCs is increased by intraocular injections of ciliary neurotrophic factor (CNTF) and axonal regeneration is further enhanced by co-injection of a cyclic AMP analogue (CPT-cAMP). Based on these data, and because cytokine signaling is negatively regulated by suppressor of cytokine signaling (SOCS) proteins, we set out to determine whether CNTF injections increase retinal SOCS expression and whether any changes are attenuated by co-injection with CPT-cAMP. Using quantitative PCR we found increased SOCS1, SOCS2 and SOCS3 mRNA levels at various times after a single CNTF injection. Expression remained high for many days. SOCS protein levels were also increased. In situ hybridization revealed that RGCs express SOCS3 mRNA, and SOCS expression in cultured RGCs was increased by CNTF. Co-injection of CPT-cAMP reduced CNTF induced expression of SOCS1 and SOCS3 mRNA and decreased SOCS3 protein expression. CNTF injection also transiently increased retinal leukemia inhibitory factor (LIF) expression, an effect that was also moderated by CPT-cAMP. We propose that, along with known reparative effects of elevated cAMP on neurons, reducing SOCS upregulation may be an additional way in which cyclic nucleotides augment cytokine-induced regenerative responses in the injured CNS.",
author = "Kevin Park and Ying Hu and Jillian Muhling and Pollett, {Margaret A.} and Dallimore, {Elizabeth J.} and Turnley, {Ann M.} and Qi Cui and Harvey, {Alan R.}",
year = "2009",
month = "6",
day = "22",
doi = "10.1016/j.mcn.2009.04.002",
language = "English",
volume = "41",
pages = "313--324",
journal = "Molecular and Cellular Neuroscience",
issn = "1044-7431",
publisher = "Academic Press Inc.",
number = "3",

}

TY - JOUR

T1 - Cytokine-induced SOCS expression is inhibited by cAMP analogue

T2 - Impact on regeneration in injured retina

AU - Park, Kevin

AU - Hu, Ying

AU - Muhling, Jillian

AU - Pollett, Margaret A.

AU - Dallimore, Elizabeth J.

AU - Turnley, Ann M.

AU - Cui, Qi

AU - Harvey, Alan R.

PY - 2009/6/22

Y1 - 2009/6/22

N2 - Injured adult retinal ganglion cells (RGCs) regrow axons into peripheral nerve (PN) grafted onto cut optic nerve. Survival and regeneration of RGCs is increased by intraocular injections of ciliary neurotrophic factor (CNTF) and axonal regeneration is further enhanced by co-injection of a cyclic AMP analogue (CPT-cAMP). Based on these data, and because cytokine signaling is negatively regulated by suppressor of cytokine signaling (SOCS) proteins, we set out to determine whether CNTF injections increase retinal SOCS expression and whether any changes are attenuated by co-injection with CPT-cAMP. Using quantitative PCR we found increased SOCS1, SOCS2 and SOCS3 mRNA levels at various times after a single CNTF injection. Expression remained high for many days. SOCS protein levels were also increased. In situ hybridization revealed that RGCs express SOCS3 mRNA, and SOCS expression in cultured RGCs was increased by CNTF. Co-injection of CPT-cAMP reduced CNTF induced expression of SOCS1 and SOCS3 mRNA and decreased SOCS3 protein expression. CNTF injection also transiently increased retinal leukemia inhibitory factor (LIF) expression, an effect that was also moderated by CPT-cAMP. We propose that, along with known reparative effects of elevated cAMP on neurons, reducing SOCS upregulation may be an additional way in which cyclic nucleotides augment cytokine-induced regenerative responses in the injured CNS.

AB - Injured adult retinal ganglion cells (RGCs) regrow axons into peripheral nerve (PN) grafted onto cut optic nerve. Survival and regeneration of RGCs is increased by intraocular injections of ciliary neurotrophic factor (CNTF) and axonal regeneration is further enhanced by co-injection of a cyclic AMP analogue (CPT-cAMP). Based on these data, and because cytokine signaling is negatively regulated by suppressor of cytokine signaling (SOCS) proteins, we set out to determine whether CNTF injections increase retinal SOCS expression and whether any changes are attenuated by co-injection with CPT-cAMP. Using quantitative PCR we found increased SOCS1, SOCS2 and SOCS3 mRNA levels at various times after a single CNTF injection. Expression remained high for many days. SOCS protein levels were also increased. In situ hybridization revealed that RGCs express SOCS3 mRNA, and SOCS expression in cultured RGCs was increased by CNTF. Co-injection of CPT-cAMP reduced CNTF induced expression of SOCS1 and SOCS3 mRNA and decreased SOCS3 protein expression. CNTF injection also transiently increased retinal leukemia inhibitory factor (LIF) expression, an effect that was also moderated by CPT-cAMP. We propose that, along with known reparative effects of elevated cAMP on neurons, reducing SOCS upregulation may be an additional way in which cyclic nucleotides augment cytokine-induced regenerative responses in the injured CNS.

UR - http://www.scopus.com/inward/record.url?scp=67349169929&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67349169929&partnerID=8YFLogxK

U2 - 10.1016/j.mcn.2009.04.002

DO - 10.1016/j.mcn.2009.04.002

M3 - Article

C2 - 19394427

AN - SCOPUS:67349169929

VL - 41

SP - 313

EP - 324

JO - Molecular and Cellular Neuroscience

JF - Molecular and Cellular Neuroscience

SN - 1044-7431

IS - 3

ER -