CCL5 (RANTES)-Induced Activation of Spinal Astrocytes can contribute to Neuroinflammation and the Maintenance of Chronic Inflammatory Pain.

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dc.contributor.advisorHolló, Krisztina
dc.contributor.advisordeptDebreceni Egyetem::Általános Orvostudományi Kar::Anatómiai, Szövet- és Fejlődéstani Intézethu_HU
dc.contributor.authorDabberha, Ali
dc.contributor.departmentDE--Általános Orvostudományi Karhu_HU
dc.contributor.opponentKöröskényi, Krisztina
dc.contributor.opponentdeptFogorvostudományi Kar, Fogorvosi Biokémiai nem önálló Tanszékhu_HU
dc.date.accessioned2022-06-10T15:26:30Z
dc.date.available2022-06-10T15:26:30Z
dc.date.created2022
dc.description.abstractThis thesis research is based on the work initiated by the previous findings of our laboratory (Gajtkó A. et al. 2020) which showed that the chemokine CCL5 is overexpressed in the spinal dorsal horn at the peak of CFA-induced inflammatory pain. In this study we wanted to complement the earlier findings with exploring the effect of CCL5 on astrocytic activation, or the “indirect” way of cytokine activity. We first investigated the mitochondrial activity of the astrocyte cultures upon treatment with CCL5 and we found significant increase when the cells were treated with 10-25 pg/ml concentrations of the chemokine, lower or higher concentrations did not change the cellular activity significantly. As a next approach to test the effect of CCL5 we studied the activation of p42/p44 MAPK which is one of the pathways activated by CCL5. Depending on the studies proving that MAPK pathways in mammalian cells transmit, intensify, and combine signals from a variety of stimulating signals to induce several physiological responses which includes inflammatory reactions. We examined astrocytic activation using CCL5 recombinant protein in a concentration that we determined in the initial experiment and we found elevated expression of pMAPK after 6 h treatment. The pMAPK immunoreactivity in the CCL5-treated cultures is mostly accumulated and increased in the perinuclear region of the astrocytes, as seen on immunofluorescent images. Finally, we intended to approach the neuroinflammatory role of CCL5-stimulation by measuring the release of the pro-inflammatory cytokine IL-1β and we found increased secretion of IL-1β upon 1h of chemokine treatment. In connection with IL-1β production we also tested the expression of NLRP2 inflammasome marker. However, NLRP2 increased only after 6h stimulation. Our results show that although CCL5 induced both IL-1β secretion and NLRP2 expression, the two are separated in time. So based on our results, the IL-1β production is most probably not a consequence of NLRP2 inflammasome activation In summary, this research proved and supported the findings suggesting the effect of the chemokine CCL5 on the astrocytic activity and its involvement in the inflammatory pathways, possibly also contributing to the maintenance of neuroinflammation and inflammatory pain. This research can contribute in discovering new perspectives for further research of pain pathways and in finding new treatments for chronic pain.hu_HU
dc.description.coursemolekuláris biológiahu_HU
dc.description.courselangangolhu_HU
dc.description.coursespecBiokémia-genomikahu_HU
dc.description.degreeMSc/MAhu_HU
dc.format.extent41hu_HU
dc.identifier.urihttp://hdl.handle.net/2437/334424
dc.language.isoenhu_HU
dc.subjectCCL5hu_HU
dc.subjectRANTEShu_HU
dc.subjectNeuroinflammationhu_HU
dc.subjectChronic Painhu_HU
dc.subjectChronic Inflammatory Painhu_HU
dc.subjectInflammatory Painhu_HU
dc.subjectSpinal Astrocyteshu_HU
dc.subject.dspaceDEENK Témalista::Orvostudományhu_HU
dc.titleCCL5 (RANTES)-Induced Activation of Spinal Astrocytes can contribute to Neuroinflammation and the Maintenance of Chronic Inflammatory Pain.hu_HU
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Theses (Faculty of Medicine)