Cytosolic Phospholipase A2-Mediated ICAM-1 Expression Is Calcium Dependent
Background. Some human malignancies such as virus-related hepatocellular cancer arise in a setting of chronic inflammation. Upregulation of ICAM-1 is a seminal late event in malignant transformation following chronic inflammation. Cytosolic phospholipase A2 (cPLA2) is a lipid-mediator activated by i...
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2001
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| Online Access: | http://hdl.handle.net/10725/2506 http://dx.doi.org/10.1006/jsre.2001.6188 http://www.sciencedirect.com/science/article/pii/S0022480401961888 |
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| _version_ | 1864513458540642304 |
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| author | Abdalla, Eddie |
| author2 | Carlton, Barnett Moore, Ernest Silliman, Christopher David, Patrick Curley, Steven |
| author2_role | author author author author author |
| author_facet | Abdalla, Eddie Carlton, Barnett Moore, Ernest Silliman, Christopher David, Patrick Curley, Steven |
| author_role | author |
| dc.creator.none.fl_str_mv | Abdalla, Eddie Carlton, Barnett Moore, Ernest Silliman, Christopher David, Patrick Curley, Steven |
| dc.date.none.fl_str_mv | 2001 2015-11-10T08:58:08Z 2015-11-10T08:58:08Z 2015-11-10 |
| dc.identifier.none.fl_str_mv | 0022-4804 http://hdl.handle.net/10725/2506 http://dx.doi.org/10.1006/jsre.2001.6188 Barnett, C. C., Moore, E. E., Silliman, C. C., Abdalla, E. K., Partrick, D. A., & Curley, S. A. (2001). Cytosolic phospholipase A 2-mediated ICAM-1 expression is calcium dependent. Journal of Surgical Research, 99(2), 307-310. http://www.sciencedirect.com/science/article/pii/S0022480401961888 |
| dc.language.none.fl_str_mv | en |
| dc.relation.none.fl_str_mv | Journal of Surgical Research |
| dc.rights.*.fl_str_mv | info:eu-repo/semantics/openAccess |
| dc.title.none.fl_str_mv | Cytosolic Phospholipase A2-Mediated ICAM-1 Expression Is Calcium Dependent |
| dc.type.none.fl_str_mv | Article info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article |
| description | Background. Some human malignancies such as virus-related hepatocellular cancer arise in a setting of chronic inflammation. Upregulation of ICAM-1 is a seminal late event in malignant transformation following chronic inflammation. Cytosolic phospholipase A2 (cPLA2) is a lipid-mediator activated by inflammatory stimuli, which has been shown to mediate ICAM-1 upregulation. As lipid mediators are known to work via calcium-dependent mechanisms in nearly all mammalian cells, we hypothesize that inflammatory-mediated ICAM-1 upregulation is dependent on both cPLA2 and intracellular calcium. Materials and methods. HUVEC were chosen as a representative cell line as they emulate hepatic sinusoids and are a well-established cell model. These were grown to confluence in T-25 flasks and stimulated with TNF-α or LPS for 6 h. Additional groups were preincubated with AACOCF3 (a specific cPLA2 inhibitor) or BAPTA A.M. (a specific inhibitor of intracellular Ca2+) prior to being exposed to inflammatory stimuli. ICAM-1 expression was determined by mean fluorescent intensity (MFI) as measured by FITC-labeled moAb to ICAM-1 via FACS. The role of intracellular Ca2+ on cPLA2 activity was determined by thin-layer chromatography. Groups were compared using ANOVA with Scheffe's post hoc analysis; *P < 0.05 vs control, †P < 0.05 vs LPS and TNF-α was considered significant; N ≥ 4 all experimental groups. Results. Both cPLA2 and Ca2+ inhibition significantly inhibited inflammatory upregulation of ICAM-1. Pretreatment with BAPTA A.M. attenuated HUVEC cPLA2 activity in response to LPS. These findings suggest that appropriate molecular target suppression may prevent malignant degeneration in the presence of chronic inflammation. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | LAURepo_6ddc35c5284e8b5bf39c37b917eebe7e |
| identifier_str_mv | 0022-4804 Barnett, C. C., Moore, E. E., Silliman, C. C., Abdalla, E. K., Partrick, D. A., & Curley, S. A. (2001). Cytosolic phospholipase A 2-mediated ICAM-1 expression is calcium dependent. Journal of Surgical Research, 99(2), 307-310. |
| language_invalid_str_mv | en |
| network_acronym_str | LAURepo |
| network_name_str | Lebanese American University repository |
| oai_identifier_str | oai:laur.lau.edu.lb:10725/2506 |
| publishDate | 2001 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| spelling | Cytosolic Phospholipase A2-Mediated ICAM-1 Expression Is Calcium DependentAbdalla, EddieCarlton, BarnettMoore, ErnestSilliman, ChristopherDavid, PatrickCurley, StevenBackground. Some human malignancies such as virus-related hepatocellular cancer arise in a setting of chronic inflammation. Upregulation of ICAM-1 is a seminal late event in malignant transformation following chronic inflammation. Cytosolic phospholipase A2 (cPLA2) is a lipid-mediator activated by inflammatory stimuli, which has been shown to mediate ICAM-1 upregulation. As lipid mediators are known to work via calcium-dependent mechanisms in nearly all mammalian cells, we hypothesize that inflammatory-mediated ICAM-1 upregulation is dependent on both cPLA2 and intracellular calcium. Materials and methods. HUVEC were chosen as a representative cell line as they emulate hepatic sinusoids and are a well-established cell model. These were grown to confluence in T-25 flasks and stimulated with TNF-α or LPS for 6 h. Additional groups were preincubated with AACOCF3 (a specific cPLA2 inhibitor) or BAPTA A.M. (a specific inhibitor of intracellular Ca2+) prior to being exposed to inflammatory stimuli. ICAM-1 expression was determined by mean fluorescent intensity (MFI) as measured by FITC-labeled moAb to ICAM-1 via FACS. The role of intracellular Ca2+ on cPLA2 activity was determined by thin-layer chromatography. Groups were compared using ANOVA with Scheffe's post hoc analysis; *P < 0.05 vs control, †P < 0.05 vs LPS and TNF-α was considered significant; N ≥ 4 all experimental groups. Results. Both cPLA2 and Ca2+ inhibition significantly inhibited inflammatory upregulation of ICAM-1. Pretreatment with BAPTA A.M. attenuated HUVEC cPLA2 activity in response to LPS. These findings suggest that appropriate molecular target suppression may prevent malignant degeneration in the presence of chronic inflammation.PublishedN/A2015-11-10T08:58:08Z2015-11-10T08:58:08Z20012015-11-10Articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article0022-4804http://hdl.handle.net/10725/2506http://dx.doi.org/10.1006/jsre.2001.6188Barnett, C. C., Moore, E. E., Silliman, C. C., Abdalla, E. K., Partrick, D. A., & Curley, S. A. (2001). Cytosolic phospholipase A 2-mediated ICAM-1 expression is calcium dependent. Journal of Surgical Research, 99(2), 307-310.http://www.sciencedirect.com/science/article/pii/S0022480401961888enJournal of Surgical Researchinfo:eu-repo/semantics/openAccessoai:laur.lau.edu.lb:10725/25062016-08-25T09:20:22Z |
| spellingShingle | Cytosolic Phospholipase A2-Mediated ICAM-1 Expression Is Calcium Dependent Abdalla, Eddie |
| status_str | publishedVersion |
| title | Cytosolic Phospholipase A2-Mediated ICAM-1 Expression Is Calcium Dependent |
| title_full | Cytosolic Phospholipase A2-Mediated ICAM-1 Expression Is Calcium Dependent |
| title_fullStr | Cytosolic Phospholipase A2-Mediated ICAM-1 Expression Is Calcium Dependent |
| title_full_unstemmed | Cytosolic Phospholipase A2-Mediated ICAM-1 Expression Is Calcium Dependent |
| title_short | Cytosolic Phospholipase A2-Mediated ICAM-1 Expression Is Calcium Dependent |
| title_sort | Cytosolic Phospholipase A2-Mediated ICAM-1 Expression Is Calcium Dependent |
| url | http://hdl.handle.net/10725/2506 http://dx.doi.org/10.1006/jsre.2001.6188 http://www.sciencedirect.com/science/article/pii/S0022480401961888 |