Autoimmune diseases are a worldwide healthcare concern. Research has focused mainly on the role of the immune system and genetic susceptibility to autoimmune disease. However, this study investigates altered target tissue properties and their contributions to the pathogenesis of induced autoimmune thyroiditis in Lewis rats. Our hypothesis was; inflammation-induced lymphocytic infiltration and subsequent fibrosis results in physical disruption of gap junctional communication in the target tissue contributing to the disease process. Our study of intercellular communication in experimentally-induced autoimmune thyroiditis (EAT) in Lewis rats revealed a deficiency in connexin expression, connexin assembly and dye transfer [(results corroborated in murine model of autoimmune thyroiditis) (AT)]. Removal of inflammatory mediators from cultures did not reestablish dye transfer despite restoration of intimate cell contact. Thus, factors other that physical disruption were influencing aberrant communication in EAT. By studying protein kinases, we found pKC activity was increased in diseased thyrocytes with enhanced expression of several pKC isozymes and induction of two disease-specific pKC isozymes. The increase in pKC activity was not due to elevated enzymatic activity, but rather to the increased levels of protein. We further found the enhanced pKC activity was responsible for the reduced Connexin 43-mediated communication observed in EAT. To determine if elevated pKC activity was linked to abnormal receptor function, we measured TSHr expression (density), and modulated pKA activity and intercellular levels of cAMP. We found diseased thyrocytes had an increased density of TSHr that was not directly linked to pKC and was not responsible for the increase in pKC activity. The TSHr linkage on the diseased cells appears to be through cAMP-pKA which we found to function normally. Clonal FRTL-5 cells were tested for use as a control for primary thyrocytes. We found that FRTL-5 cells do not express Connexin 43 protein and mRNA, or communicate suggesting that the absence of Connexin 43 may be responsible for the aberrancies in thyroid function noted in FRTL-5 cells. A pKC-mediated loss of coordinated thyroid function contributes to AT and hypothyroidism. Clearly, the identification of disease-causing factors that result in a sustained participation of target tissue in EAT will be a significant accomplishment.
","abstract_html":"<p>Autoimmune diseases are a worldwide healthcare concern. Research has focused mainly on the role of the immune system and genetic susceptibility to autoimmune disease. However, this study investigates altered target tissue properties and their contributions to the pathogenesis of induced autoimmune thyroiditis in Lewis rats. Our hypothesis was; inflammation-induced lymphocytic infiltration and subsequent fibrosis results in physical disruption of gap junctional communication in the target tissue contributing to the disease process. Our study of intercellular communication in experimentally-induced autoimmune thyroiditis (EAT) in Lewis rats revealed a deficiency in connexin expression, connexin assembly and dye transfer [(results corroborated in murine model of autoimmune thyroiditis) (AT)]. Removal of inflammatory mediators from cultures did not reestablish dye transfer despite restoration of intimate cell contact. Thus, factors other that physical disruption were influencing aberrant communication in EAT. By studying protein kinases, we found pKC activity was increased in diseased thyrocytes with enhanced expression of several pKC isozymes and induction of two disease-specific pKC isozymes. The increase in pKC activity was not due to elevated enzymatic activity, but rather to the increased levels of protein. We further found the enhanced pKC activity was responsible for the reduced Connexin 43-mediated communication observed in EAT. To determine if elevated pKC activity was linked to abnormal receptor function, we measured TSHr expression (density), and modulated pKA activity and intercellular levels of cAMP. We found diseased thyrocytes had an increased density of TSHr that was not directly linked to pKC and was not responsible for the increase in pKC activity. The TSHr linkage on the diseased cells appears to be through cAMP-pKA which we found to function normally. Clonal FRTL-5 cells were tested for use as a control for primary thyrocytes. We found that FRTL-5 cells do not express Connexin 43 protein and mRNA, or communicate suggesting that the absence of Connexin 43 may be responsible for the aberrancies in thyroid function noted in FRTL-5 cells. A pKC-mediated loss of coordinated thyroid function contributes to AT and hypothyroidism. Clearly, the identification of disease-causing factors that result in a sustained participation of target tissue in EAT will be a significant accomplishment.</p>","abstract_has_math":false,"creators":["Lazarus, Joyce P."],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation","degree_discipline":"Physiology","degree_department":null,"school":null,"contributors":["Lora M. Green","Richard R. A. Luben","Subburaman Mohan","Jerald Nelson","Robert W. Teel"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":1996,"date_issued":"1996-12-01T08:00:00Z","date_published":"1996-12-01T08:00:00Z","updated_at":"2026-07-24T02:53:37Z","subjects":["Physiology","Autoimmune Diseases -- physiopathology; Cell Communication; Protein Kinase C; Thyroiditis, Autoimmune; Thyrotropin; Receptors, Thyroid Hormone."],"languages":["English"],"rights":["This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://scholarsrepository.llu.edu/etd/899","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Lora M. Green","Richard R. A. Luben","Subburaman Mohan","Jerald Nelson","Robert W. 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The author retains all other copyrights."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://scholarsrepository.llu.edu/etd/899"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Autoimmune diseases are a worldwide healthcare concern. Research has focused mainly on the role of the immune system and genetic susceptibility to autoimmune disease. However, this study investigates altered target tissue properties and their contributions to the pathogenesis of induced autoimmune thyroiditis in Lewis rats. Our hypothesis was; inflammation-induced lymphocytic infiltration and subsequent fibrosis results in physical disruption of gap junctional communication in the target tissue contributing to the disease process. Our study of intercellular communication in experimentally-induced autoimmune thyroiditis (EAT) in Lewis rats revealed a deficiency in connexin expression, connexin assembly and dye transfer [(results corroborated in murine model of autoimmune thyroiditis) (AT)]. Removal of inflammatory mediators from cultures did not reestablish dye transfer despite restoration of intimate cell contact. Thus, factors other that physical disruption were influencing aberrant communication in EAT. By studying protein kinases, we found pKC activity was increased in diseased thyrocytes with enhanced expression of several pKC isozymes and induction of two disease-specific pKC isozymes. The increase in pKC activity was not due to elevated enzymatic activity, but rather to the increased levels of protein. We further found the enhanced pKC activity was responsible for the reduced Connexin 43-mediated communication observed in EAT. To determine if elevated pKC activity was linked to abnormal receptor function, we measured TSHr expression (density), and modulated pKA activity and intercellular levels of cAMP. We found diseased thyrocytes had an increased density of TSHr that was not directly linked to pKC and was not responsible for the increase in pKC activity. The TSHr linkage on the diseased cells appears to be through cAMP-pKA which we found to function normally. Clonal FRTL-5 cells were tested for use as a control for primary thyrocytes. We found that FRTL-5 cells do not express Connexin 43 protein and mRNA, or communicate suggesting that the absence of Connexin 43 may be responsible for the aberrancies in thyroid function noted in FRTL-5 cells. A pKC-mediated loss of coordinated thyroid function contributes to AT and hypothyroidism. Clearly, the identification of disease-causing factors that result in a sustained participation of target tissue in EAT will be a significant accomplishment.
"]},{"key":"dc:title","label":"Title","values":["Aberrant Communication and Protein Kinase C in Experimental Autoimmune Thyroiditis"]}]}],"canonical_facts":{"dc:contributor":["Lora M. Green","Richard R. A. Luben","Subburaman Mohan","Jerald Nelson","Robert W. Teel"],"dc:creator":["Lazarus, Joyce P."],"dc:description.abstract":["Autoimmune diseases are a worldwide healthcare concern. Research has focused mainly on the role of the immune system and genetic susceptibility to autoimmune disease. However, this study investigates altered target tissue properties and their contributions to the pathogenesis of induced autoimmune thyroiditis in Lewis rats. Our hypothesis was; inflammation-induced lymphocytic infiltration and subsequent fibrosis results in physical disruption of gap junctional communication in the target tissue contributing to the disease process. Our study of intercellular communication in experimentally-induced autoimmune thyroiditis (EAT) in Lewis rats revealed a deficiency in connexin expression, connexin assembly and dye transfer [(results corroborated in murine model of autoimmune thyroiditis) (AT)]. Removal of inflammatory mediators from cultures did not reestablish dye transfer despite restoration of intimate cell contact. Thus, factors other that physical disruption were influencing aberrant communication in EAT. By studying protein kinases, we found pKC activity was increased in diseased thyrocytes with enhanced expression of several pKC isozymes and induction of two disease-specific pKC isozymes. The increase in pKC activity was not due to elevated enzymatic activity, but rather to the increased levels of protein. We further found the enhanced pKC activity was responsible for the reduced Connexin 43-mediated communication observed in EAT. To determine if elevated pKC activity was linked to abnormal receptor function, we measured TSHr expression (density), and modulated pKA activity and intercellular levels of cAMP. We found diseased thyrocytes had an increased density of TSHr that was not directly linked to pKC and was not responsible for the increase in pKC activity. The TSHr linkage on the diseased cells appears to be through cAMP-pKA which we found to function normally. Clonal FRTL-5 cells were tested for use as a control for primary thyrocytes. We found that FRTL-5 cells do not express Connexin 43 protein and mRNA, or communicate suggesting that the absence of Connexin 43 may be responsible for the aberrancies in thyroid function noted in FRTL-5 cells. A pKC-mediated loss of coordinated thyroid function contributes to AT and hypothyroidism. Clearly, the identification of disease-causing factors that result in a sustained participation of target tissue in EAT will be a significant accomplishment.
"],"dc:identifier":["https://scholarsrepository.llu.edu/etd/899"],"dc:language":["English"],"dc:rights":["This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights."],"dc:subject":["Physiology","Autoimmune Diseases -- physiopathology; Cell Communication; Protein Kinase C; Thyroiditis, Autoimmune; Thyrotropin; Receptors, Thyroid Hormone."],"dc:title":["Aberrant Communication and Protein Kinase C in Experimental Autoimmune Thyroiditis"],"thesis:degree_discipline":["Physiology"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T02:53:37Z"}