Celecoxib alleviates nociceptor sensitization mediated by interleukin-1beta-primed annulus fibrosus cells
Purpose This study aims to analyze the effect of pro-inflammatory cytokine-stimulated human annulus fibrosus cells (hAFCs) on the sensitization of dorsal root ganglion (DRG) cells. We further hypothesized that celecoxib (cxb) could inhibit hAFCs-induced DRG sensitization. Methods hAFCs from spinal t...
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| Veröffentlicht in: | European spine journal 2023-06, Vol.32 (6), p.2048-2058 |
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| creator | Ma, Junxuan Häne, Surya Eglauf, Janick Pfannkuche, Judith Soubrier, Astrid Li, Zhen Peroglio, Marianna Hoppe, Sven Benneker, Lorin Lang, Gernot Wangler, Sebastian Alini, Mauro Creemers, Laura B. Grad, Sibylle Häckel, Sonja |
| description | Purpose
This study aims to analyze the effect of pro-inflammatory cytokine-stimulated human annulus fibrosus cells (hAFCs) on the sensitization of dorsal root ganglion (DRG) cells. We further hypothesized that celecoxib (cxb) could inhibit hAFCs-induced DRG sensitization.
Methods
hAFCs from spinal trauma patients were stimulated with TNF-α or IL-1β. Cxb was added on day 2. On day 4, the expression of pro-inflammatory and neurotrophic genes was evaluated using RT-qPCR. Levels of prostaglandin E2 (PGE-2), IL-8, and IL-6 were measured in the conditioned medium (CM) using ELISA. hAFCs CM was then applied to stimulate the DRG cell line (ND7/23) for 6 days. Then, calcium imaging (Fluo4) was performed to evaluate DRG cell sensitization. Both spontaneous and bradykinin-stimulated (0.5 μM) calcium responses were analyzed. The effects on primary bovine DRG cell culture were performed in parallel to the DRG cell line model.
Results
IL-1ß stimulation significantly enhanced the release of PGE-2 in hAFCs CM, while this increase was completely suppressed by 10 µM cxb. hAFCs revealed elevated IL-6 and IL-8 release following TNF-α and IL-1β treatment, though cxb did not alter this. The effect of hAFCs CM on DRG cell sensitization was influenced by adding cxb to hAFCs; both the DRG cell line and primary bovine DRG nociceptors showed a lower sensitivity to bradykinin stimulation.
Conclusion
Cxb can inhibit PGE-2 production in hAFCs in an IL-1β-induced pro-inflammatory in vitro environment. The cxb applied to the hAFCs also reduces the sensitization of DRG nociceptors that are stimulated by the hAFCs CM. |
| doi_str_mv | 10.1007/s00586-023-07672-x |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_hal_p</sourceid><recordid>TN_cdi_hal_primary_oai_HAL_emse_04167524v1</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2821486167</sourcerecordid><originalsourceid>FETCH-LOGICAL-c454t-66f0a07e9e9b6c77f56048f894ccf7bcdac835f859b33456cd067f94df76aff3</originalsourceid><addsrcrecordid>eNp9kU9v1DAQxS0EotvCF-CAInFBlQzj-G-O1Qoo0kpcerccZwwuXmeJk2rLp8dLSpE4cPJI_s2bN_MIecXgHQPQ7wuANIpCyylopVt6fEI2TPCWQsfbp2QDnQCqNOvOyHkptwBMdqCekzOuQTMm1YbELSb04zH2jUsJ76KbsTR59NHjYR6npmAucY4_3RzH3OxxOBFD0983Mc84JVy-x0xZj7OjhylWoHE5L2kpTYj9NJZaeEypvCDPgksFXz68F-Tm44eb7TXdffn0eXu1o15IMVOlAjjQ2GHXK691kAqECaYT3gfd-8F5w2Uwsus5F1L5AZQOnRiCVi4EfkEuV9lvLtmTITfd29FFe321s7gvaEEwpWUr7liF367wYRp_LFhmu4_l5NZlHJdiWwOtMQakqOibf9DbcZly3aRSLRNGVdVKtSvl6-ZlwvBogYE9hWbX0GwNzf4OzR5r0-sH6aWv93ts-ZNSBfgKlPqVv-L0d_Z_ZH8BTLqkIQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2821486167</pqid></control><display><type>article</type><title>Celecoxib alleviates nociceptor sensitization mediated by interleukin-1beta-primed annulus fibrosus cells</title><source>MEDLINE</source><source>SpringerNature Journals</source><creator>Ma, Junxuan ; Häne, Surya ; Eglauf, Janick ; Pfannkuche, Judith ; Soubrier, Astrid ; Li, Zhen ; Peroglio, Marianna ; Hoppe, Sven ; Benneker, Lorin ; Lang, Gernot ; Wangler, Sebastian ; Alini, Mauro ; Creemers, Laura B. ; Grad, Sibylle ; Häckel, Sonja</creator><creatorcontrib>Ma, Junxuan ; Häne, Surya ; Eglauf, Janick ; Pfannkuche, Judith ; Soubrier, Astrid ; Li, Zhen ; Peroglio, Marianna ; Hoppe, Sven ; Benneker, Lorin ; Lang, Gernot ; Wangler, Sebastian ; Alini, Mauro ; Creemers, Laura B. ; Grad, Sibylle ; Häckel, Sonja</creatorcontrib><description>Purpose
This study aims to analyze the effect of pro-inflammatory cytokine-stimulated human annulus fibrosus cells (hAFCs) on the sensitization of dorsal root ganglion (DRG) cells. We further hypothesized that celecoxib (cxb) could inhibit hAFCs-induced DRG sensitization.
Methods
hAFCs from spinal trauma patients were stimulated with TNF-α or IL-1β. Cxb was added on day 2. On day 4, the expression of pro-inflammatory and neurotrophic genes was evaluated using RT-qPCR. Levels of prostaglandin E2 (PGE-2), IL-8, and IL-6 were measured in the conditioned medium (CM) using ELISA. hAFCs CM was then applied to stimulate the DRG cell line (ND7/23) for 6 days. Then, calcium imaging (Fluo4) was performed to evaluate DRG cell sensitization. Both spontaneous and bradykinin-stimulated (0.5 μM) calcium responses were analyzed. The effects on primary bovine DRG cell culture were performed in parallel to the DRG cell line model.
Results
IL-1ß stimulation significantly enhanced the release of PGE-2 in hAFCs CM, while this increase was completely suppressed by 10 µM cxb. hAFCs revealed elevated IL-6 and IL-8 release following TNF-α and IL-1β treatment, though cxb did not alter this. The effect of hAFCs CM on DRG cell sensitization was influenced by adding cxb to hAFCs; both the DRG cell line and primary bovine DRG nociceptors showed a lower sensitivity to bradykinin stimulation.
Conclusion
Cxb can inhibit PGE-2 production in hAFCs in an IL-1β-induced pro-inflammatory in vitro environment. The cxb applied to the hAFCs also reduces the sensitization of DRG nociceptors that are stimulated by the hAFCs CM.</description><identifier>ISSN: 0940-6719</identifier><identifier>EISSN: 1432-0932</identifier><identifier>DOI: 10.1007/s00586-023-07672-x</identifier><identifier>PMID: 37071156</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Animals ; Annulus Fibrosus ; Back pain ; Bioengineering ; Bradykinin ; Bradykinin - pharmacology ; Calcium - pharmacology ; Calcium imaging ; Cattle ; Celecoxib ; Celecoxib - pharmacology ; Cell culture ; Cells ; Cells, Cultured ; Cytokines ; Dorsal root ganglia ; Enzymes ; Ganglia, Spinal ; Gene expression ; Human health and pathology ; Humans ; IL-1β ; Inflammation ; Interleukin 6 ; Interleukin 8 ; Interleukin-1beta - pharmacology ; Interleukin-8 - pharmacology ; Life Sciences ; Medicine ; Medicine & Public Health ; Neurosurgery ; Nociceptors ; Original Article ; Pain perception ; Prostaglandin E2 ; Surgical Orthopedics ; Tumor Necrosis Factor-alpha ; Tumor necrosis factor-TNF ; Tumor necrosis factor-α</subject><ispartof>European spine journal, 2023-06, Vol.32 (6), p.2048-2058</ispartof><rights>The Author(s) 2023</rights><rights>2023. The Author(s).</rights><rights>The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Attribution</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c454t-66f0a07e9e9b6c77f56048f894ccf7bcdac835f859b33456cd067f94df76aff3</citedby><cites>FETCH-LOGICAL-c454t-66f0a07e9e9b6c77f56048f894ccf7bcdac835f859b33456cd067f94df76aff3</cites><orcidid>0000-0001-8923-9832 ; 0000-0001-9552-3653 ; 0000-0002-5458-3446 ; 0000-0001-6526-0151 ; 0000-0003-0685-1909 ; 0000-0002-5320-5638 ; 0000-0003-0166-5525 ; 0000-0002-9415-6633</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00586-023-07672-x$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00586-023-07672-x$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37071156$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal-emse.ccsd.cnrs.fr/emse-04167524$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Ma, Junxuan</creatorcontrib><creatorcontrib>Häne, Surya</creatorcontrib><creatorcontrib>Eglauf, Janick</creatorcontrib><creatorcontrib>Pfannkuche, Judith</creatorcontrib><creatorcontrib>Soubrier, Astrid</creatorcontrib><creatorcontrib>Li, Zhen</creatorcontrib><creatorcontrib>Peroglio, Marianna</creatorcontrib><creatorcontrib>Hoppe, Sven</creatorcontrib><creatorcontrib>Benneker, Lorin</creatorcontrib><creatorcontrib>Lang, Gernot</creatorcontrib><creatorcontrib>Wangler, Sebastian</creatorcontrib><creatorcontrib>Alini, Mauro</creatorcontrib><creatorcontrib>Creemers, Laura B.</creatorcontrib><creatorcontrib>Grad, Sibylle</creatorcontrib><creatorcontrib>Häckel, Sonja</creatorcontrib><title>Celecoxib alleviates nociceptor sensitization mediated by interleukin-1beta-primed annulus fibrosus cells</title><title>European spine journal</title><addtitle>Eur Spine J</addtitle><addtitle>Eur Spine J</addtitle><description>Purpose
This study aims to analyze the effect of pro-inflammatory cytokine-stimulated human annulus fibrosus cells (hAFCs) on the sensitization of dorsal root ganglion (DRG) cells. We further hypothesized that celecoxib (cxb) could inhibit hAFCs-induced DRG sensitization.
Methods
hAFCs from spinal trauma patients were stimulated with TNF-α or IL-1β. Cxb was added on day 2. On day 4, the expression of pro-inflammatory and neurotrophic genes was evaluated using RT-qPCR. Levels of prostaglandin E2 (PGE-2), IL-8, and IL-6 were measured in the conditioned medium (CM) using ELISA. hAFCs CM was then applied to stimulate the DRG cell line (ND7/23) for 6 days. Then, calcium imaging (Fluo4) was performed to evaluate DRG cell sensitization. Both spontaneous and bradykinin-stimulated (0.5 μM) calcium responses were analyzed. The effects on primary bovine DRG cell culture were performed in parallel to the DRG cell line model.
Results
IL-1ß stimulation significantly enhanced the release of PGE-2 in hAFCs CM, while this increase was completely suppressed by 10 µM cxb. hAFCs revealed elevated IL-6 and IL-8 release following TNF-α and IL-1β treatment, though cxb did not alter this. The effect of hAFCs CM on DRG cell sensitization was influenced by adding cxb to hAFCs; both the DRG cell line and primary bovine DRG nociceptors showed a lower sensitivity to bradykinin stimulation.
Conclusion
Cxb can inhibit PGE-2 production in hAFCs in an IL-1β-induced pro-inflammatory in vitro environment. The cxb applied to the hAFCs also reduces the sensitization of DRG nociceptors that are stimulated by the hAFCs CM.</description><subject>Animals</subject><subject>Annulus Fibrosus</subject><subject>Back pain</subject><subject>Bioengineering</subject><subject>Bradykinin</subject><subject>Bradykinin - pharmacology</subject><subject>Calcium - pharmacology</subject><subject>Calcium imaging</subject><subject>Cattle</subject><subject>Celecoxib</subject><subject>Celecoxib - pharmacology</subject><subject>Cell culture</subject><subject>Cells</subject><subject>Cells, Cultured</subject><subject>Cytokines</subject><subject>Dorsal root ganglia</subject><subject>Enzymes</subject><subject>Ganglia, Spinal</subject><subject>Gene expression</subject><subject>Human health and pathology</subject><subject>Humans</subject><subject>IL-1β</subject><subject>Inflammation</subject><subject>Interleukin 6</subject><subject>Interleukin 8</subject><subject>Interleukin-1beta - pharmacology</subject><subject>Interleukin-8 - pharmacology</subject><subject>Life Sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Neurosurgery</subject><subject>Nociceptors</subject><subject>Original Article</subject><subject>Pain perception</subject><subject>Prostaglandin E2</subject><subject>Surgical Orthopedics</subject><subject>Tumor Necrosis Factor-alpha</subject><subject>Tumor necrosis factor-TNF</subject><subject>Tumor necrosis factor-α</subject><issn>0940-6719</issn><issn>1432-0932</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9kU9v1DAQxS0EotvCF-CAInFBlQzj-G-O1Qoo0kpcerccZwwuXmeJk2rLp8dLSpE4cPJI_s2bN_MIecXgHQPQ7wuANIpCyylopVt6fEI2TPCWQsfbp2QDnQCqNOvOyHkptwBMdqCekzOuQTMm1YbELSb04zH2jUsJ76KbsTR59NHjYR6npmAucY4_3RzH3OxxOBFD0983Mc84JVy-x0xZj7OjhylWoHE5L2kpTYj9NJZaeEypvCDPgksFXz68F-Tm44eb7TXdffn0eXu1o15IMVOlAjjQ2GHXK691kAqECaYT3gfd-8F5w2Uwsus5F1L5AZQOnRiCVi4EfkEuV9lvLtmTITfd29FFe321s7gvaEEwpWUr7liF367wYRp_LFhmu4_l5NZlHJdiWwOtMQakqOibf9DbcZly3aRSLRNGVdVKtSvl6-ZlwvBogYE9hWbX0GwNzf4OzR5r0-sH6aWv93ts-ZNSBfgKlPqVv-L0d_Z_ZH8BTLqkIQ</recordid><startdate>20230601</startdate><enddate>20230601</enddate><creator>Ma, Junxuan</creator><creator>Häne, Surya</creator><creator>Eglauf, Janick</creator><creator>Pfannkuche, Judith</creator><creator>Soubrier, Astrid</creator><creator>Li, Zhen</creator><creator>Peroglio, Marianna</creator><creator>Hoppe, Sven</creator><creator>Benneker, Lorin</creator><creator>Lang, Gernot</creator><creator>Wangler, Sebastian</creator><creator>Alini, Mauro</creator><creator>Creemers, Laura B.</creator><creator>Grad, Sibylle</creator><creator>Häckel, Sonja</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><general>Springer Verlag</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0001-8923-9832</orcidid><orcidid>https://orcid.org/0000-0001-9552-3653</orcidid><orcidid>https://orcid.org/0000-0002-5458-3446</orcidid><orcidid>https://orcid.org/0000-0001-6526-0151</orcidid><orcidid>https://orcid.org/0000-0003-0685-1909</orcidid><orcidid>https://orcid.org/0000-0002-5320-5638</orcidid><orcidid>https://orcid.org/0000-0003-0166-5525</orcidid><orcidid>https://orcid.org/0000-0002-9415-6633</orcidid></search><sort><creationdate>20230601</creationdate><title>Celecoxib alleviates nociceptor sensitization mediated by interleukin-1beta-primed annulus fibrosus cells</title><author>Ma, Junxuan ; Häne, Surya ; Eglauf, Janick ; Pfannkuche, Judith ; Soubrier, Astrid ; Li, Zhen ; Peroglio, Marianna ; Hoppe, Sven ; Benneker, Lorin ; Lang, Gernot ; Wangler, Sebastian ; Alini, Mauro ; Creemers, Laura B. ; Grad, Sibylle ; Häckel, Sonja</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c454t-66f0a07e9e9b6c77f56048f894ccf7bcdac835f859b33456cd067f94df76aff3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Animals</topic><topic>Annulus Fibrosus</topic><topic>Back pain</topic><topic>Bioengineering</topic><topic>Bradykinin</topic><topic>Bradykinin - pharmacology</topic><topic>Calcium - pharmacology</topic><topic>Calcium imaging</topic><topic>Cattle</topic><topic>Celecoxib</topic><topic>Celecoxib - pharmacology</topic><topic>Cell culture</topic><topic>Cells</topic><topic>Cells, Cultured</topic><topic>Cytokines</topic><topic>Dorsal root ganglia</topic><topic>Enzymes</topic><topic>Ganglia, Spinal</topic><topic>Gene expression</topic><topic>Human health and pathology</topic><topic>Humans</topic><topic>IL-1β</topic><topic>Inflammation</topic><topic>Interleukin 6</topic><topic>Interleukin 8</topic><topic>Interleukin-1beta - pharmacology</topic><topic>Interleukin-8 - pharmacology</topic><topic>Life Sciences</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Neurosurgery</topic><topic>Nociceptors</topic><topic>Original Article</topic><topic>Pain perception</topic><topic>Prostaglandin E2</topic><topic>Surgical Orthopedics</topic><topic>Tumor Necrosis Factor-alpha</topic><topic>Tumor necrosis factor-TNF</topic><topic>Tumor necrosis factor-α</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ma, Junxuan</creatorcontrib><creatorcontrib>Häne, Surya</creatorcontrib><creatorcontrib>Eglauf, Janick</creatorcontrib><creatorcontrib>Pfannkuche, Judith</creatorcontrib><creatorcontrib>Soubrier, Astrid</creatorcontrib><creatorcontrib>Li, Zhen</creatorcontrib><creatorcontrib>Peroglio, Marianna</creatorcontrib><creatorcontrib>Hoppe, Sven</creatorcontrib><creatorcontrib>Benneker, Lorin</creatorcontrib><creatorcontrib>Lang, Gernot</creatorcontrib><creatorcontrib>Wangler, Sebastian</creatorcontrib><creatorcontrib>Alini, Mauro</creatorcontrib><creatorcontrib>Creemers, Laura B.</creatorcontrib><creatorcontrib>Grad, Sibylle</creatorcontrib><creatorcontrib>Häckel, Sonja</creatorcontrib><collection>SpringerOpen</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>European spine journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ma, Junxuan</au><au>Häne, Surya</au><au>Eglauf, Janick</au><au>Pfannkuche, Judith</au><au>Soubrier, Astrid</au><au>Li, Zhen</au><au>Peroglio, Marianna</au><au>Hoppe, Sven</au><au>Benneker, Lorin</au><au>Lang, Gernot</au><au>Wangler, Sebastian</au><au>Alini, Mauro</au><au>Creemers, Laura B.</au><au>Grad, Sibylle</au><au>Häckel, Sonja</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Celecoxib alleviates nociceptor sensitization mediated by interleukin-1beta-primed annulus fibrosus cells</atitle><jtitle>European spine journal</jtitle><stitle>Eur Spine J</stitle><addtitle>Eur Spine J</addtitle><date>2023-06-01</date><risdate>2023</risdate><volume>32</volume><issue>6</issue><spage>2048</spage><epage>2058</epage><pages>2048-2058</pages><issn>0940-6719</issn><eissn>1432-0932</eissn><abstract>Purpose
This study aims to analyze the effect of pro-inflammatory cytokine-stimulated human annulus fibrosus cells (hAFCs) on the sensitization of dorsal root ganglion (DRG) cells. We further hypothesized that celecoxib (cxb) could inhibit hAFCs-induced DRG sensitization.
Methods
hAFCs from spinal trauma patients were stimulated with TNF-α or IL-1β. Cxb was added on day 2. On day 4, the expression of pro-inflammatory and neurotrophic genes was evaluated using RT-qPCR. Levels of prostaglandin E2 (PGE-2), IL-8, and IL-6 were measured in the conditioned medium (CM) using ELISA. hAFCs CM was then applied to stimulate the DRG cell line (ND7/23) for 6 days. Then, calcium imaging (Fluo4) was performed to evaluate DRG cell sensitization. Both spontaneous and bradykinin-stimulated (0.5 μM) calcium responses were analyzed. The effects on primary bovine DRG cell culture were performed in parallel to the DRG cell line model.
Results
IL-1ß stimulation significantly enhanced the release of PGE-2 in hAFCs CM, while this increase was completely suppressed by 10 µM cxb. hAFCs revealed elevated IL-6 and IL-8 release following TNF-α and IL-1β treatment, though cxb did not alter this. The effect of hAFCs CM on DRG cell sensitization was influenced by adding cxb to hAFCs; both the DRG cell line and primary bovine DRG nociceptors showed a lower sensitivity to bradykinin stimulation.
Conclusion
Cxb can inhibit PGE-2 production in hAFCs in an IL-1β-induced pro-inflammatory in vitro environment. The cxb applied to the hAFCs also reduces the sensitization of DRG nociceptors that are stimulated by the hAFCs CM.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>37071156</pmid><doi>10.1007/s00586-023-07672-x</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0001-8923-9832</orcidid><orcidid>https://orcid.org/0000-0001-9552-3653</orcidid><orcidid>https://orcid.org/0000-0002-5458-3446</orcidid><orcidid>https://orcid.org/0000-0001-6526-0151</orcidid><orcidid>https://orcid.org/0000-0003-0685-1909</orcidid><orcidid>https://orcid.org/0000-0002-5320-5638</orcidid><orcidid>https://orcid.org/0000-0003-0166-5525</orcidid><orcidid>https://orcid.org/0000-0002-9415-6633</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0940-6719 |
| ispartof | European spine journal, 2023-06, Vol.32 (6), p.2048-2058 |
| issn | 0940-6719 1432-0932 |
| language | eng |
| recordid | cdi_hal_primary_oai_HAL_emse_04167524v1 |
| source | MEDLINE; SpringerNature Journals |
| subjects | Animals Annulus Fibrosus Back pain Bioengineering Bradykinin Bradykinin - pharmacology Calcium - pharmacology Calcium imaging Cattle Celecoxib Celecoxib - pharmacology Cell culture Cells Cells, Cultured Cytokines Dorsal root ganglia Enzymes Ganglia, Spinal Gene expression Human health and pathology Humans IL-1β Inflammation Interleukin 6 Interleukin 8 Interleukin-1beta - pharmacology Interleukin-8 - pharmacology Life Sciences Medicine Medicine & Public Health Neurosurgery Nociceptors Original Article Pain perception Prostaglandin E2 Surgical Orthopedics Tumor Necrosis Factor-alpha Tumor necrosis factor-TNF Tumor necrosis factor-α |
| title | Celecoxib alleviates nociceptor sensitization mediated by interleukin-1beta-primed annulus fibrosus cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-20T15%3A44%3A37IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_hal_p&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Celecoxib%20alleviates%20nociceptor%20sensitization%20mediated%20by%20interleukin-1beta-primed%20annulus%20fibrosus%20cells&rft.jtitle=European%20spine%20journal&rft.au=Ma,%20Junxuan&rft.date=2023-06-01&rft.volume=32&rft.issue=6&rft.spage=2048&rft.epage=2058&rft.pages=2048-2058&rft.issn=0940-6719&rft.eissn=1432-0932&rft_id=info:doi/10.1007/s00586-023-07672-x&rft_dat=%3Cproquest_hal_p%3E2821486167%3C/proquest_hal_p%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2821486167&rft_id=info:pmid/37071156&rfr_iscdi=true |