Inflammatory Bowel Disease (IBD) affects over 1 million Americans and can cause severe tissue damage and even death. TNF-α is a pro-inflammatory cytokine that is elevated in IBD and plays a central role in inflammation. Previous results in our laboratory showed that another cytokine, IL-1β, induces chemokine expression in intestinal epithelial cells (IEC), which is mediated by Rho-associated kinase (ROCK). Because ROCK may be an important mediator of inflammation, we extended our investigations to examine the role of ROCK in TNF-α-stimulated chemokine responses in IEC. Inhibiting ROCK with the Y-27632 compound resulted in a significant, but incomplete, suppression of TNF-α-induced CXCL8 expression in Caco-2 cells, indicating that ROCK is required for optimal CXCL8 production in IEC. ROCK inhibition also blocked TNF-α-stimulated JNK phosphorylation in Caco-2 cells but did not affect NF-κB activation, suggesting an explanation for the partial suppression of CXCL8, as CXCL8 is under the control of both NF-κB and the JNK-activated AP-1 transcription factor. Unlike CXCL8, the production of TNF-α-induced CCL2 and CCL20 expression was enhanced by ROCK inhibition in Caco-2 cells, indicating that ROCK activity had a suppressive effect on these responses. Further experiments showed that the ROCK-dependent suppression was likely mediated by ERK since the MEK/ERK inhibitor, PD98059, had the same enhancement effect as the ROCK inhibitor on TNF-α-induced CCL2 secretion. These results suggest that ROCK plays a complex role in chemokine production in IEC. Furthermore, since ROCK appears to control the expression of several pro-inflammatory mediators, ROCK may be a promising therapeutic target for IBD.
","abstract_html":"<p>Inflammatory Bowel Disease (IBD) affects over 1 million Americans and can cause severe tissue damage and even death. TNF-α is a pro-inflammatory cytokine that is elevated in IBD and plays a central role in inflammation. Previous results in our laboratory showed that another cytokine, IL-1β, induces chemokine expression in intestinal epithelial cells (IEC), which is mediated by Rho-associated kinase (ROCK). Because ROCK may be an important mediator of inflammation, we extended our investigations to examine the role of ROCK in TNF-α-stimulated chemokine responses in IEC. Inhibiting ROCK with the Y-27632 compound resulted in a significant, but incomplete, suppression of TNF-α-induced CXCL8 expression in Caco-2 cells, indicating that ROCK is required for optimal CXCL8 production in IEC. ROCK inhibition also blocked TNF-α-stimulated JNK phosphorylation in Caco-2 cells but did not affect NF-κB activation, suggesting an explanation for the partial suppression of CXCL8, as CXCL8 is under the control of both NF-κB and the JNK-activated AP-1 transcription factor. Unlike CXCL8, the production of TNF-α-induced CCL2 and CCL20 expression was enhanced by ROCK inhibition in Caco-2 cells, indicating that ROCK activity had a suppressive effect on these responses. Further experiments showed that the ROCK-dependent suppression was likely mediated by ERK since the MEK/ERK inhibitor, PD98059, had the same enhancement effect as the ROCK inhibitor on TNF-α-induced CCL2 secretion. These results suggest that ROCK plays a complex role in chemokine production in IEC. Furthermore, since ROCK appears to control the expression of several pro-inflammatory mediators, ROCK may be a promising therapeutic target for IBD.</p>","abstract_has_math":false,"creators":["Perey, Aaron C"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation","degree_discipline":null,"degree_department":null,"school":null,"contributors":["Dennis W. McGee"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2017,"date_issued":"2017-05-21T07:00:00Z","date_published":"2017-05-21T07:00:00Z","updated_at":"2026-07-24T01:10:09Z","subjects":["Intestinal epithelial cells","CXCL8","TNF-alpha","CCL2","IL-8","MCP-1","ROCK","IL-1","inflammation","IBD"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://orb.binghamton.edu/dissertation_and_theses/16","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Dennis W. McGee"]},{"key":"dc:creator","label":"Author","values":["Perey, Aaron C"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2017-06-12T07:00:00Z"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Intestinal epithelial cells","CXCL8","TNF-alpha","CCL2","IL-8","MCP-1","ROCK","IL-1","inflammation","IBD"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://orb.binghamton.edu/dissertation_and_theses/16"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Inflammatory Bowel Disease (IBD) affects over 1 million Americans and can cause severe tissue damage and even death. TNF-α is a pro-inflammatory cytokine that is elevated in IBD and plays a central role in inflammation. Previous results in our laboratory showed that another cytokine, IL-1β, induces chemokine expression in intestinal epithelial cells (IEC), which is mediated by Rho-associated kinase (ROCK). Because ROCK may be an important mediator of inflammation, we extended our investigations to examine the role of ROCK in TNF-α-stimulated chemokine responses in IEC. Inhibiting ROCK with the Y-27632 compound resulted in a significant, but incomplete, suppression of TNF-α-induced CXCL8 expression in Caco-2 cells, indicating that ROCK is required for optimal CXCL8 production in IEC. ROCK inhibition also blocked TNF-α-stimulated JNK phosphorylation in Caco-2 cells but did not affect NF-κB activation, suggesting an explanation for the partial suppression of CXCL8, as CXCL8 is under the control of both NF-κB and the JNK-activated AP-1 transcription factor. Unlike CXCL8, the production of TNF-α-induced CCL2 and CCL20 expression was enhanced by ROCK inhibition in Caco-2 cells, indicating that ROCK activity had a suppressive effect on these responses. Further experiments showed that the ROCK-dependent suppression was likely mediated by ERK since the MEK/ERK inhibitor, PD98059, had the same enhancement effect as the ROCK inhibitor on TNF-α-induced CCL2 secretion. These results suggest that ROCK plays a complex role in chemokine production in IEC. Furthermore, since ROCK appears to control the expression of several pro-inflammatory mediators, ROCK may be a promising therapeutic target for IBD.
"]},{"key":"dc:title","label":"Title","values":["The role of the rho-associated coiled-coil containing kinase (ROCK) in cytokine-induced chemokine responses in intestinal epithelial cells"]}]}],"canonical_facts":{"dc:contributor":["Dennis W. McGee"],"dc:creator":["Perey, Aaron C"],"dc:date.available":["2017-06-12T07:00:00Z"],"dc:description.abstract":["Inflammatory Bowel Disease (IBD) affects over 1 million Americans and can cause severe tissue damage and even death. TNF-α is a pro-inflammatory cytokine that is elevated in IBD and plays a central role in inflammation. Previous results in our laboratory showed that another cytokine, IL-1β, induces chemokine expression in intestinal epithelial cells (IEC), which is mediated by Rho-associated kinase (ROCK). Because ROCK may be an important mediator of inflammation, we extended our investigations to examine the role of ROCK in TNF-α-stimulated chemokine responses in IEC. Inhibiting ROCK with the Y-27632 compound resulted in a significant, but incomplete, suppression of TNF-α-induced CXCL8 expression in Caco-2 cells, indicating that ROCK is required for optimal CXCL8 production in IEC. ROCK inhibition also blocked TNF-α-stimulated JNK phosphorylation in Caco-2 cells but did not affect NF-κB activation, suggesting an explanation for the partial suppression of CXCL8, as CXCL8 is under the control of both NF-κB and the JNK-activated AP-1 transcription factor. Unlike CXCL8, the production of TNF-α-induced CCL2 and CCL20 expression was enhanced by ROCK inhibition in Caco-2 cells, indicating that ROCK activity had a suppressive effect on these responses. Further experiments showed that the ROCK-dependent suppression was likely mediated by ERK since the MEK/ERK inhibitor, PD98059, had the same enhancement effect as the ROCK inhibitor on TNF-α-induced CCL2 secretion. These results suggest that ROCK plays a complex role in chemokine production in IEC. Furthermore, since ROCK appears to control the expression of several pro-inflammatory mediators, ROCK may be a promising therapeutic target for IBD.
"],"dc:identifier":["https://orb.binghamton.edu/dissertation_and_theses/16"],"dc:subject":["Intestinal epithelial cells","CXCL8","TNF-alpha","CCL2","IL-8","MCP-1","ROCK","IL-1","inflammation","IBD"],"dc:title":["The role of the rho-associated coiled-coil containing kinase (ROCK) in cytokine-induced chemokine responses in intestinal epithelial cells"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T01:10:09Z"}