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Title: The role of NF-kB transcription factor in the regulation of cytokine induced thermal hyperalgesia in a leishmania major model in BALB/c mice
Authors: Hoblos, Reem
Advisors: Karam, Marc 
Keywords: Hyperalgesia, L. major, CEL, TNF-α, IL-1β, IL-10, NF-kB
Subjects: Hyperalgesia
Dissertations, Academic
University of Balamand--Dissertations
Issue Date: 2021
Sustained hypernociception is considered to be a hallmark of several inflammatory diseases. Association between hyperalgesia and the secretion of a soup of cytokines has been the subject of many recent investigations in several disease models. Leishmania major (L. major) induced cutaneous leishmaniasis is one of the trending models to study such a correlation with several research finding the upregulations of TNF-α, IL-1β and IL-10 among others involved in regulating such pain nociception. Hitherto, very few studies have addressed the molecular mechanisms orchestrating such a response in L. major model of pain.
In this research, we inspect the role of the transcription factor (TF) NF-kB in the modulation of L. major prompted hyperalgesia and cytokine expression in BALB/c mice through the administration of celastrol (CEL) a potent blocker of this TF. Intraperitoneal injection of CEL was able to attenuate the L. major induced thermal hyperalgesia in BALB/c mice for 15 days for the dose of 0.5 mg/kg and 21 days for 1 mg/kg dosage as detected by hot plate and tail flick behavioral assessments. Cytokines levels were quantified in the infected paws of BALB/c mice using Sandwich ELISA. Only the administration of 1 mg/kg CEL was able to decrease TNF-α levels in L. major infected mice for 23 days. IL-1β expression declined significantly with the administration of both CEL concentrations in L. major infected mice all through 23 days. No significant levels of IL-10 was detected in our experimental groups. The activation of NF-kB was detected through observing the levels of phosphorylation of p65 subunit using PathScan phospho-ELISA. High degree of NF-kB phosphorylation was detected in L. major infected BALB/c mice. The phosphorylation of NF-kB p65 was suppressed by 1 mg/kg CEL alone. Collectively, our results provide new insights on the correlation between the activation of NF-kB, the induction of thermal hyperalgesia and the expression of TNF-α and IL-1β in L. major model of cutaneous nociception.
Includes bibliographical references (p. 52-72)
Rights: This object is protected by copyright, and is made available here for research and educational purposes. Permission to reuse, publish, or reproduce the object beyond the personal and educational use exceptions must be obtained from the copyright holder
Ezproxy URL: Link to full text
Type: Thesis
Appears in Collections:UOB Theses and Projects

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