Interleukin-10 (IL-10) is an important anti-inflammatory cytokine acting to dampen macrophage activation during and after the immune response to microbial pathogens. During the innate immune response to gram-negative bacteria, macrophages are triggered to produce numerous pro-inflammatory mediators through Toll-like receptor 4 (TLR4) binding to lipopolysaccharide (LPS). IL-10 acts on these cells through the induced expression of genes that inhibit expression of select TLR-induced pro-inflammatory genes. Our understanding of the mechanisms by which cells respond to IL-10 with the anti-inflammatory response remains incomplete. Herein, I investigated the IL-10-induced transcriptional response that occurs in TLR-activated macrophages. I analyzed the kinetic profile of expression for a group of genes induced by IL-10 in a manner that depends on synergy with TLR signaling (referred to as IL-10 super-induced genes). IL-10 induces the expression of these target genes in three distinct temporal waves - first, primary response genes, followed by early secondary response genes, and then late secondary response genes. All of the IL-10 super-induced genes appear to be expressed through an increase in their transcription rate. Thus, the IL-10 anti-inflammatory response in macrophages involves specific crosstalk between IL-10 and TLR signaling leading to a transcriptional cascade of distinct waves of anti-inflammatory gene expression.
","abstract_html":"<p>Interleukin-10 (IL-10) is an important anti-inflammatory cytokine acting to dampen macrophage activation during and after the immune response to microbial pathogens. During the innate immune response to gram-negative bacteria, macrophages are triggered to produce numerous pro-inflammatory mediators through Toll-like receptor 4 (TLR4) binding to lipopolysaccharide (LPS). IL-10 acts on these cells through the induced expression of genes that inhibit expression of select TLR-induced pro-inflammatory genes. Our understanding of the mechanisms by which cells respond to IL-10 with the anti-inflammatory response remains incomplete. Herein, I investigated the IL-10-induced transcriptional response that occurs in TLR-activated macrophages. I analyzed the kinetic profile of expression for a group of genes induced by IL-10 in a manner that depends on synergy with TLR signaling (referred to as IL-10 super-induced genes). IL-10 induces the expression of these target genes in three distinct temporal waves - first, primary response genes, followed by early secondary response genes, and then late secondary response genes. All of the IL-10 super-induced genes appear to be expressed through an increase in their transcription rate. Thus, the IL-10 anti-inflammatory response in macrophages involves specific crosstalk between IL-10 and TLR signaling leading to a transcriptional cascade of distinct waves of anti-inflammatory gene expression.</p>","abstract_has_math":false,"creators":["Smith, Tyler Joseph"],"institution":null,"degree_name":"Master of Science in Biology","degree_level":"Masters","degree_discipline":"Biology","degree_department":null,"school":null,"contributors":["Brian Weaver"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2013,"date_issued":"2013-01-01T08:00:00Z","date_published":"2013-01-01T08:00:00Z","updated_at":"2026-07-24T03:16:23Z","subjects":["innate immunity","toll-like receptor","LPS","IL-10","macrophages","inflammation","cytokines","transcription","signal transduction","signaling crosstalk","Biology"],"languages":[],"rights":["© Tyler Joseph Smith"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://bearworks.missouristate.edu/theses/1310","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Brian Weaver"]},{"key":"dc:creator","label":"Author","values":["Smith, Tyler Joseph"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"thesis:degree_discipline","label":"Discipline","values":["Biology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Masters"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Master of Science in Biology"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["innate immunity","toll-like receptor","LPS","IL-10","macrophages","inflammation","cytokines","transcription","signal transduction","signaling crosstalk","Biology"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:rights","label":"Dc Rights","values":["© Tyler Joseph Smith"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://bearworks.missouristate.edu/theses/1310"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Interleukin-10 (IL-10) is an important anti-inflammatory cytokine acting to dampen macrophage activation during and after the immune response to microbial pathogens. During the innate immune response to gram-negative bacteria, macrophages are triggered to produce numerous pro-inflammatory mediators through Toll-like receptor 4 (TLR4) binding to lipopolysaccharide (LPS). IL-10 acts on these cells through the induced expression of genes that inhibit expression of select TLR-induced pro-inflammatory genes. Our understanding of the mechanisms by which cells respond to IL-10 with the anti-inflammatory response remains incomplete. Herein, I investigated the IL-10-induced transcriptional response that occurs in TLR-activated macrophages. I analyzed the kinetic profile of expression for a group of genes induced by IL-10 in a manner that depends on synergy with TLR signaling (referred to as IL-10 super-induced genes). IL-10 induces the expression of these target genes in three distinct temporal waves - first, primary response genes, followed by early secondary response genes, and then late secondary response genes. All of the IL-10 super-induced genes appear to be expressed through an increase in their transcription rate. Thus, the IL-10 anti-inflammatory response in macrophages involves specific crosstalk between IL-10 and TLR signaling leading to a transcriptional cascade of distinct waves of anti-inflammatory gene expression.
"]},{"key":"dc:title","label":"Title","values":["Temporal Transcriptional Regulation of IL-10-Induced Anti-Inflammatory Genes in LPS-Triggered Macrophages"]}]}],"canonical_facts":{"dc:contributor":["Brian Weaver"],"dc:creator":["Smith, Tyler Joseph"],"dc:description.abstract":["Interleukin-10 (IL-10) is an important anti-inflammatory cytokine acting to dampen macrophage activation during and after the immune response to microbial pathogens. During the innate immune response to gram-negative bacteria, macrophages are triggered to produce numerous pro-inflammatory mediators through Toll-like receptor 4 (TLR4) binding to lipopolysaccharide (LPS). IL-10 acts on these cells through the induced expression of genes that inhibit expression of select TLR-induced pro-inflammatory genes. Our understanding of the mechanisms by which cells respond to IL-10 with the anti-inflammatory response remains incomplete. Herein, I investigated the IL-10-induced transcriptional response that occurs in TLR-activated macrophages. I analyzed the kinetic profile of expression for a group of genes induced by IL-10 in a manner that depends on synergy with TLR signaling (referred to as IL-10 super-induced genes). IL-10 induces the expression of these target genes in three distinct temporal waves - first, primary response genes, followed by early secondary response genes, and then late secondary response genes. All of the IL-10 super-induced genes appear to be expressed through an increase in their transcription rate. Thus, the IL-10 anti-inflammatory response in macrophages involves specific crosstalk between IL-10 and TLR signaling leading to a transcriptional cascade of distinct waves of anti-inflammatory gene expression.
"],"dc:identifier":["https://bearworks.missouristate.edu/theses/1310"],"dc:rights":["© Tyler Joseph Smith"],"dc:subject":["innate immunity","toll-like receptor","LPS","IL-10","macrophages","inflammation","cytokines","transcription","signal transduction","signaling crosstalk","Biology"],"dc:title":["Temporal Transcriptional Regulation of IL-10-Induced Anti-Inflammatory Genes in LPS-Triggered Macrophages"],"thesis:degree_discipline":["Biology"],"thesis:degree_level":["Masters"],"thesis:degree_name":["Master of Science in Biology"]},"updated_at":"2026-07-24T03:16:23Z"}