a 2009

Satellite glial cells synthesize IL-6 and express signal-transducing receptors to mediate IL-6 effect in the rat neuropathic pain model

DUBOVÝ, Petr, Ilona KLUSÁKOVÁ, Ivana HRADILOVÁ SVÍŽENSKÁ and Václav BRÁZDA

Basic information

Original name

Satellite glial cells synthesize IL-6 and express signal-transducing receptors to mediate IL-6 effect in the rat neuropathic pain model

Name in Czech

Satelitní gliové buňky syntetizují IL-6 a exprimují signál transdukující receptory ke zprostředkování účinku IL-6 u potkaního modelu neuropatické bolesti

Authors

DUBOVÝ, Petr, Ilona KLUSÁKOVÁ, Ivana HRADILOVÁ SVÍŽENSKÁ and Václav BRÁZDA

Edition

9th European Meeting on Glial Cells in Health and Disease, 2009

Other information

Language

English

Type of outcome

Konferenční abstrakt

Field of Study

30000 3. Medical and Health Sciences

Country of publisher

France

Confidentiality degree

není předmětem státního či obchodního tajemství

Organization unit

Faculty of Medicine

UT WoS

000270075500545

Keywords (in Czech)

behaviorální testy; ganglion dorzálního kořene; gp130 receptor; IL-6; IL-6 receptor; neuropatická bolest; periferní nervová soustava; satelitní gliové buňky; signál transdukující receptory; STAT3; unilaterální konstrikce sciatického nervu

Keywords in English

behavioral tests; dorsal root ganglion; gp130 receptor; IL-6; IL-6 receptor; neuropathic pain; peripheral nervous system; satellite glial cells; signal-transducing receptors; STAT3; unilateral constriction of sciatic nerve

Tags

International impact
Změněno: 26/1/2010 12:23, Mgr. Marek David, Ph.D.

Abstract

V originále

Many experimental studies have documented important role of cytokines during different types of neuropathy and their potential to induce or facilitate neuropathic pain. Interleukin-6 (IL-6) is a proinflammatory cytokine involved as a key signal molecule in the neuronal and immune responses to nerve injury. A biological effect of IL-6 is mediated by two signal-transducing receptors: glycoprotein 130 (gp130) and IL-6 receptor (IL6r). The gp130 receptor is a transmembrane glycoprotein and integral part of STAT3 signaling pathway. We have investigated immunohistochemical localization of IL-6, gp130, IL6r and activated STAT3 in both ipsilateral and contralateral lumbar (L4-5) and cervical (C7-8) dorsal root ganglia (DRG) following chronic constriction injury (CCI) of sciatic nerve. Immunostaining for glutamine synthetase (GS) and ED-1 were used for detection of satellite glial cells (SGC) and macrophages, respectively. In addition, in situ hybridization was used to prove IL-6 synthesis in DRG. Twenty eight male rats were operated on triple unilateral ligation of right sciatic nerve (CCI) and allowed to survive for 1, 3, 7 and 14 days. All surgical procedures were performed aseptically under deep anesthesia by a xylazine and ketamine. To test neuropathic pain induction, withdrawal threshold of mechanoallodynia and thermal hyperalgesia was measured by Dynamic plantar aesthesiometer (UGO BASILE) and Plantar test (UGO BASILE), respectively. Immunohistochemical and in situ hybridization results revealed that besides neurons SGC of DRG associated with injured nerve are source of IL-6 protein. Bilateral elevation of immunostaining for IL-6r in SGC was detected only in L4-5 DRG 1 week from CCI. In contrast to naïve DRG, enhanced immunoreactivity for gp130 and STAT3 was present in SGC of both C7-8 and L4-5 DRG following unilateral CCI. The results suggest that unilateral nerve injury used as neuropathic pain model induces synthesis of IL-6 and its IL-6r in the SGC of DRG associated with injured nerve. Therefore, biological effects of IL-6 during neuropathic pain are probably driven by IL-6r, because gp130 and activated STAT3 are expressed by SGC of both cervical and lumbal segments.

In Czech

Many experimental studies have documented important role of cytokines during different types of neuropathy and their potential to induce or facilitate neuropathic pain. Interleukin-6 (IL-6) is a proinflammatory cytokine involved as a key signal molecule in the neuronal and immune responses to nerve injury. A biological effect of IL-6 is mediated by two signal-transducing receptors: glycoprotein 130 (gp130) and IL-6 receptor (IL6r). The gp130 receptor is a transmembrane glycoprotein and integral part of STAT3 signaling pathway. We have investigated immunohistochemical localization of IL-6, gp130, IL6r and activated STAT3 in both ipsilateral and contralateral lumbar (L4-5) and cervical (C7-8) dorsal root ganglia (DRG) following chronic constriction injury (CCI) of sciatic nerve. Immunostaining for glutamine synthetase (GS) and ED-1 were used for detection of satellite glial cells (SGC) and macrophages, respectively. In addition, in situ hybridization was used to prove IL-6 synthesis in DRG. Twenty eight male rats were operated on triple unilateral ligation of right sciatic nerve (CCI) and allowed to survive for 1, 3, 7 and 14 days. All surgical procedures were performed aseptically under deep anesthesia by a xylazine and ketamine. To test neuropathic pain induction, withdrawal threshold of mechanoallodynia and thermal hyperalgesia was measured by Dynamic plantar aesthesiometer (UGO BASILE) and Plantar test (UGO BASILE), respectively. Immunohistochemical and in situ hybridization results revealed that besides neurons SGC of DRG associated with injured nerve are source of IL-6 protein. Bilateral elevation of immunostaining for IL-6r in SGC was detected only in L4-5 DRG 1 week from CCI. In contrast to naïve DRG, enhanced immunoreactivity for gp130 and STAT3 was present in SGC of both C7-8 and L4-5 DRG following unilateral CCI. The results suggest that unilateral nerve injury used as neuropathic pain model induces synthesis of IL-6 and its IL-6r in the SGC of DRG associated with injured nerve. Therefore, biological effects of IL-6 during neuropathic pain are probably driven by IL-6r, because gp130 and activated STAT3 are expressed by SGC of both cervical and lumbal segments.

Links

GA309/07/0121, research and development project
Name: Změny cytokinů ve spinálních gangliích experimentálních modelů neuropatické bolesti indukované unilaterálním poškozením nervu
Investor: Czech Science Foundation, Spatio-temporal changes of cytokines in the dorsal root ganglia of experimental neuropathic pain models induced by unilateral nerve injury
MSM0021622404, plan (intention)
Name: Vnitřní organizace a neurobiologické mechanismy funkčních systémů CNS
Investor: Ministry of Education, Youth and Sports of the CR, The internal organisation and neurobiological mechanisms of functional CNS systems under normal and pathological conditions.