CCAAT/enhancer-binding protein (C/EBP) &beta and C/EBP&delta are known to participate in the regulation of many genes associated with inflammation. However, little is known about the activation and function of C/EBP&beta and -&delta in inflammatory responses elicited by Fc&gamma receptor (Fc&gammaR) activation. Here I showed that C/EBP&beta and -&delta activation were induced in immunoglobulin G immune complex (IgG IC)-treated macrophages by using gel shift assays. The increased expression of C/EBP&beta and -&delta occurred at both mRNA and protein levels. Furthermore, induction of C/EBP&beta and -&delta was mediated, to a large extent, by activating Fc&gammaRs. Using small interfering RNA (siRNA)-mediated knockdown as well as macrophages deficient for C/EBP&beta and/or -&delta, I demonstrated that C/EBP&beta and -&delta played a critical role in the production of tumor necrosis factor-&alpha (TNF-&alpha), macrophage inflammatory protein-2 (MIP-2), and macrophage inflammatory protein-1&alpha (MIP-1&alpha) in IgG IC-stimulated macrophages. Moreover, both extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen activated protein kinase (MAPK) were involved in C/EBP induction and TNF-&alpha, MIP-2, and MIP-1&alpha production induced by IgG IC. I provided the evidence that complement component 5a (C5a) regulated IgG immune complex-induced inflammatory responses in macrophages by enhancing ERK1/2 and p38 MAPK activities as well as C/EBP&beta and -delta activities. To further explore the roles of C/EBP&beta and C/EBP&delta in Fc&gammaR-mediated inflammatory responses in vivo, I used IgG IC-induced acute lung injury model. I showed that both C/EBP&beta and C/EBP&delta activation were triggered in lungs challenged by IgG IC. I further demonstrated that C/EBP&beta but not C/EBP&delta deficient mice displayed significant attenuation of pulmonary vascular permeability and neutrophil accumulation when compared with wild type mice. Moreover, C/EBP&beta deficient mice expressed considerable less inflammatory mediators compared with wild type littermates. Together, these data indicate that both C/EBP&beta and C/EBP&delta act as inflammatory stimulators in vitro during IgG IC-mediated inflammation. However, it is C/EBP&beta but not C/EBP&delta depletion attenuates IgG IC-induced lung inflammatory reactions in vivo.
","abstract_html":"<p>CCAAT/enhancer-binding protein (C/EBP) &beta and C/EBP&delta are known to participate in the regulation of many genes associated with inflammation. However, little is known about the activation and function of C/EBP&beta and -&delta in inflammatory responses elicited by Fc&gamma receptor (Fc&gammaR) activation. Here I showed that C/EBP&beta and -&delta activation were induced in immunoglobulin G immune complex (IgG IC)-treated macrophages by using gel shift assays. The increased expression of C/EBP&beta and -&delta occurred at both mRNA and protein levels. Furthermore, induction of C/EBP&beta and -&delta was mediated, to a large extent, by activating Fc&gammaRs. Using small interfering RNA (siRNA)-mediated knockdown as well as macrophages deficient for C/EBP&beta and/or -&delta, I demonstrated that C/EBP&beta and -&delta played a critical role in the production of tumor necrosis factor-&alpha (TNF-&alpha), macrophage inflammatory protein-2 (MIP-2), and macrophage inflammatory protein-1&alpha (MIP-1&alpha) in IgG IC-stimulated macrophages. Moreover, both extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen activated protein kinase (MAPK) were involved in C/EBP induction and TNF-&alpha, MIP-2, and MIP-1&alpha production induced by IgG IC. I provided the evidence that complement component 5a (C5a) regulated IgG immune complex-induced inflammatory responses in macrophages by enhancing ERK1/2 and p38 MAPK activities as well as C/EBP&beta and -delta activities. To further explore the roles of C/EBP&beta and C/EBP&delta in Fc&gammaR-mediated inflammatory responses in vivo, I used IgG IC-induced acute lung injury model. I showed that both C/EBP&beta and C/EBP&delta activation were triggered in lungs challenged by IgG IC. I further demonstrated that C/EBP&beta but not C/EBP&delta deficient mice displayed significant attenuation of pulmonary vascular permeability and neutrophil accumulation when compared with wild type mice. Moreover, C/EBP&beta deficient mice expressed considerable less inflammatory mediators compared with wild type littermates. Together, these data indicate that both C/EBP&beta and C/EBP&delta act as inflammatory stimulators in vitro during IgG IC-mediated inflammation. However, it is C/EBP&beta but not C/EBP&delta depletion attenuates IgG IC-induced lung inflammatory reactions in vivo.</p>","abstract_has_math":false,"creators":["Yan, Chunguang"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation","degree_discipline":"Biomedical Sciences","degree_department":null,"school":null,"contributors":["Hongwei Gao"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2012,"date_issued":"2012-01-01T08:00:00Z","date_published":"2012-01-01T08:00:00Z","updated_at":"2026-07-24T03:26:24Z","subjects":[],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://commons.und.edu/theses/1388","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Hongwei Gao"]},{"key":"dc:creator","label":"Author","values":["Yan, Chunguang"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"thesis:degree_discipline","label":"Discipline","values":["Biomedical Sciences"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://commons.und.edu/theses/1388"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["CCAAT/enhancer-binding protein (C/EBP) &beta and C/EBP&delta are known to participate in the regulation of many genes associated with inflammation. However, little is known about the activation and function of C/EBP&beta and -&delta in inflammatory responses elicited by Fc&gamma receptor (Fc&gammaR) activation. Here I showed that C/EBP&beta and -&delta activation were induced in immunoglobulin G immune complex (IgG IC)-treated macrophages by using gel shift assays. The increased expression of C/EBP&beta and -&delta occurred at both mRNA and protein levels. Furthermore, induction of C/EBP&beta and -&delta was mediated, to a large extent, by activating Fc&gammaRs. Using small interfering RNA (siRNA)-mediated knockdown as well as macrophages deficient for C/EBP&beta and/or -&delta, I demonstrated that C/EBP&beta and -&delta played a critical role in the production of tumor necrosis factor-&alpha (TNF-&alpha), macrophage inflammatory protein-2 (MIP-2), and macrophage inflammatory protein-1&alpha (MIP-1&alpha) in IgG IC-stimulated macrophages. Moreover, both extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen activated protein kinase (MAPK) were involved in C/EBP induction and TNF-&alpha, MIP-2, and MIP-1&alpha production induced by IgG IC. I provided the evidence that complement component 5a (C5a) regulated IgG immune complex-induced inflammatory responses in macrophages by enhancing ERK1/2 and p38 MAPK activities as well as C/EBP&beta and -delta activities. To further explore the roles of C/EBP&beta and C/EBP&delta in Fc&gammaR-mediated inflammatory responses in vivo, I used IgG IC-induced acute lung injury model. I showed that both C/EBP&beta and C/EBP&delta activation were triggered in lungs challenged by IgG IC. I further demonstrated that C/EBP&beta but not C/EBP&delta deficient mice displayed significant attenuation of pulmonary vascular permeability and neutrophil accumulation when compared with wild type mice. Moreover, C/EBP&beta deficient mice expressed considerable less inflammatory mediators compared with wild type littermates. Together, these data indicate that both C/EBP&beta and C/EBP&delta act as inflammatory stimulators in vitro during IgG IC-mediated inflammation. However, it is C/EBP&beta but not C/EBP&delta depletion attenuates IgG IC-induced lung inflammatory reactions in vivo.
"]},{"key":"dc:title","label":"Title","values":["Roles of CCAAT/enhancer-binding protein [beta] and [-delta] in immunoglobulin G immune complex-induced Inflammation"]}]}],"canonical_facts":{"dc:contributor":["Hongwei Gao"],"dc:creator":["Yan, Chunguang"],"dc:description.abstract":["CCAAT/enhancer-binding protein (C/EBP) &beta and C/EBP&delta are known to participate in the regulation of many genes associated with inflammation. However, little is known about the activation and function of C/EBP&beta and -&delta in inflammatory responses elicited by Fc&gamma receptor (Fc&gammaR) activation. Here I showed that C/EBP&beta and -&delta activation were induced in immunoglobulin G immune complex (IgG IC)-treated macrophages by using gel shift assays. The increased expression of C/EBP&beta and -&delta occurred at both mRNA and protein levels. Furthermore, induction of C/EBP&beta and -&delta was mediated, to a large extent, by activating Fc&gammaRs. Using small interfering RNA (siRNA)-mediated knockdown as well as macrophages deficient for C/EBP&beta and/or -&delta, I demonstrated that C/EBP&beta and -&delta played a critical role in the production of tumor necrosis factor-&alpha (TNF-&alpha), macrophage inflammatory protein-2 (MIP-2), and macrophage inflammatory protein-1&alpha (MIP-1&alpha) in IgG IC-stimulated macrophages. Moreover, both extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen activated protein kinase (MAPK) were involved in C/EBP induction and TNF-&alpha, MIP-2, and MIP-1&alpha production induced by IgG IC. I provided the evidence that complement component 5a (C5a) regulated IgG immune complex-induced inflammatory responses in macrophages by enhancing ERK1/2 and p38 MAPK activities as well as C/EBP&beta and -delta activities. To further explore the roles of C/EBP&beta and C/EBP&delta in Fc&gammaR-mediated inflammatory responses in vivo, I used IgG IC-induced acute lung injury model. I showed that both C/EBP&beta and C/EBP&delta activation were triggered in lungs challenged by IgG IC. I further demonstrated that C/EBP&beta but not C/EBP&delta deficient mice displayed significant attenuation of pulmonary vascular permeability and neutrophil accumulation when compared with wild type mice. Moreover, C/EBP&beta deficient mice expressed considerable less inflammatory mediators compared with wild type littermates. Together, these data indicate that both C/EBP&beta and C/EBP&delta act as inflammatory stimulators in vitro during IgG IC-mediated inflammation. However, it is C/EBP&beta but not C/EBP&delta depletion attenuates IgG IC-induced lung inflammatory reactions in vivo.
"],"dc:identifier":["https://commons.und.edu/theses/1388"],"dc:title":["Roles of CCAAT/enhancer-binding protein [beta] and [-delta] in immunoglobulin G immune complex-induced Inflammation"],"thesis:degree_discipline":["Biomedical Sciences"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T03:26:24Z"}