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csu1345752316.pdf (869.17 KB)
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CCL2 (MCP-1) MEDIATES CHRONIC PELVIC PAIN THROUGH MAST CELLS IN EXPERIMENTAL AUTOIMMUNE CYSTITIS
Author Info
Bicer, Fuat
Permalink:
http://rave.ohiolink.edu/etdc/view?acc_num=csu1345752316
Abstract Details
Year and Degree
2012, Doctor of Philosophy in Clinical-Bioanalytical Chemistry, Cleveland State University, College of Sciences and Health Professions.
Abstract
Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic inflammatory bladder condition with unknown pathophysiology. Chronic pelvic pain is one of the most important and disturbing symptoms of IC/PBS, beside urinary frequency, urgency, and nocturia. Increased amounts of mast cells (MCs) and CCL2 have been found in bladder tissue and urine, respectively. Whether or not there is a causal relationship between CCL2, MCs, and pelvic pain in IC/PBS is unknown. Methods: Female BALB/c mice were immunized with a peptide consisting of residues 65-84 of the bladder urothelium-specific protein uroplakin 3A to induce experimental autoimmune cystitis (EAC), a model for human IC/PBS. Referred visceral pelvic pain was measured using von Frey monofilaments at different times after immunization. Lidocaine was instilled into the bladder, colon and uterus to locate the source of the pelvic pain. CCL2 expression in tissues was measured by qRT-PCR and ELISA, and MCs in the bladder were quantified by toluidine blue staining. An MC stabilizer (cromolyn sodium), histamine H1 receptor blocker (cetirizine), and histamine H2 receptor blocker (ranitidine) were administered orally to show the relation of MCs with the pain. CCL2-/- and CCR2-/- mice, and CCR2 (CCL2 receptor) antagonist treatment were used to delineate the causative effect of CCL2 on MC accumulation and chronic pelvic pain. Results: All mice immunized with the uroplakin 3A peptide developed pelvic pain within 5 days and up to 40 days after immunization. Lidocaine alleviated the pain only when it was installed into the bladder of EAC mice, confirming the bladder origin of the pain. The amounts of CCL2 mRNA and protein, and the numbers of MCs were markedly increased in bladder tissue up to 40 days after immunization with peptide compared with controls. Administrations of cromolyn sodium and ranitidine significantly decreased pelvic pain in the model. Moreover, immunization did not establish chronic pelvic pain or accumulation of MCs in MCP-1-/- or CCR2-/- mice, compared with wild type mice. Conclusion: CCL2 has a vital role in causing chronic pelvic pain through accumulation of MCs in this newly created EAC mouse model, and might be an essential player in the pathogenesis of human IC/PBS.
Committee
Firouz Daneshgari, MD (Committee Chair)
Yan XU, PhD (Committee Member)
Vincent K. Tuohy, PhD (Committee Member)
Xiaoxia Li, PhD (Committee Member)
Aimin Zhou, PhD (Committee Member)
Cengiz Z. Altuntas, PhD (Committee Member)
Pages
138 p.
Subject Headings
Biochemistry
;
Biology
;
Health Sciences
;
Medicine
;
Molecular Biology
;
Neurosciences
Keywords
CCL2
;
MCP-1
;
Chronic Pelvic Pain
;
Mast Cell
;
Experimental Autoimmune Cystitis
;
IC PBS
;
Uroplakin 3A
;
Bladder
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Citations
Bicer, F. (2012).
CCL2 (MCP-1) MEDIATES CHRONIC PELVIC PAIN THROUGH MAST CELLS IN EXPERIMENTAL AUTOIMMUNE CYSTITIS
[Doctoral dissertation, Cleveland State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=csu1345752316
APA Style (7th edition)
Bicer, Fuat.
CCL2 (MCP-1) MEDIATES CHRONIC PELVIC PAIN THROUGH MAST CELLS IN EXPERIMENTAL AUTOIMMUNE CYSTITIS.
2012. Cleveland State University, Doctoral dissertation.
OhioLINK Electronic Theses and Dissertations Center
, http://rave.ohiolink.edu/etdc/view?acc_num=csu1345752316.
MLA Style (8th edition)
Bicer, Fuat. "CCL2 (MCP-1) MEDIATES CHRONIC PELVIC PAIN THROUGH MAST CELLS IN EXPERIMENTAL AUTOIMMUNE CYSTITIS." Doctoral dissertation, Cleveland State University, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=csu1345752316
Chicago Manual of Style (17th edition)
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Document number:
csu1345752316
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988
Copyright Info
© 2012, all rights reserved.
This open access ETD is published by Cleveland State University and OhioLINK.