Academic Journal
In vitro sepsis up-regulates Nociceptin/Orphanin FQ receptor expression and function on human T- but not B-cells
| العنوان: | In vitro sepsis up-regulates Nociceptin/Orphanin FQ receptor expression and function on human T- but not B-cells |
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| المؤلفون: | Bird, Mark F, Hebbes, Christopher P, Tamang, Anushuya, Willets, Jonathon Mark, Thompson, Jonathan P, Guerrini, Remo, Calo, Girolamo, Lambert, David G |
| المساهمون: | Bird, Mark F, Hebbes, Christopher P, Tamang, Anushuya, Willets, Jonathon Mark, Thompson, Jonathan P, Guerrini, Remo, Calo, Girolamo, Lambert, David G |
| سنة النشر: | 2023 |
| المجموعة: | Padua Research Archive (IRIS - Università degli Studi di Padova) |
| مصطلحات موضوعية: | B-cell, NOP receptor, Nociceptin/Orphanin FQ, T-cell, biosensor, confocal microscopy, sepsis |
| الوصف: | Background and purpose: In animal models of sepsis, increased activation of the Nociceptin/Orphanin FQ (N/OFQ) receptor NOP is associated with mortality and NOP antagonists improved survival. We have explored the role of the N/OFQ-NOP system in freshly isolated volunteer human B- and T-cells incubated with lipopolysaccharide (LPS) and peptidoglycan G (PepG) as a model of in vitro sepsis. Experimental approach: B- and T-cell NOP expression was measured using the NOP fluorescent probe N/OFQATTO594 , N/OFQ content was measured using immunofluorescence, N/OFQ release was tracked using a CHOhNOPGαiq5 biosensor assay and NOP function was measured using transwell migration and cytokine/chemokine release using a 25-plex assay format. Cells were challenged with LPS/PepG. Key results: CD19-positive B-cells bound N/OFQATTO594 ; they also contain N/OFQ. Stimulation with CXCL13/IL-4 increased N/OFQ release. N/OFQ trended to reduced migration to CXCL13/IL-4. Surface NOP expression was unaffected by LPS/PepG, but this treatment increased GM-CSF release in an N/OFQ sensitive manner. CD3-positive T-cells did not bind N/OFQATTO594 ; they did contain N/OFQ. Stimulation with CXCL12/IL-6 increased N/OFQ release. When incubated with LPS/PepG, NOP surface expression was induced leading to N/OFQATTO594 binding. In LPS/PepG-treated cells, N/OFQ reduced migration to CXCL12/IL-6. LPS/PepG increased GM-CSF release in an N/OFQ sensitive manner. Conclusions and implications: We suggest both a constitutive and sepsis-inducible N/OFQ-NOP receptor autocrine regulation of B- and T-cell function, respectively. These NOP receptors variably inhibit migration and reduce GM-CSF release. These data provide mechanistic insights to the detrimental role for increased N/OFQ signalling in sepsis and suggest a potential role for NOP antagonists as treatments. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/37021779; info:eu-repo/semantics/altIdentifier/wos/WOS:000985152200001; journal:BRITISH JOURNAL OF PHARMACOLOGY; https://hdl.handle.net/11577/3479489; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85159088974 |
| DOI: | 10.1111/bph.16088 |
| الاتاحة: | https://hdl.handle.net/11577/3479489 https://doi.org/10.1111/bph.16088 |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.E1A6F243 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1111/bph.16088 |
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