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Protein kinase Czeta (PKCzeta) regulates ocular inflammation and apoptosis in endotoxin-induced uveitis (EIU): signaling molecules involved in EIU resolution by PKCzeta inhibitor and interleukin-13.
Am J Pathol. 2007 Apr; 170(4):1241-57.AJ

Abstract

We show that inhibitory effect of interleukin-13 on endotoxin-induced uveitis in the Lewis rat is dependent on signaling activity of protein kinase Czeta (PKCzeta). To understand the effect of interleukin-13 or PKCzeta inhibitor treatment, the activation status of rat bone marrow-derived macrophages was studied in vitro. At 6 hours, lipopolysaccharide-stimulated macrophages produced tumor necrosis factor-alpha (TNF-alpha) with nuclear factor kappaB (NF-kappaB)/p65 expression. Treatment led to absence of NF-kappaB/p65 expression and low levels of TNF-alpha, suggesting accelerated inactivation of macrophages. At 24 hours after lipopolysaccharide stimulation, nuclear NF-kappaB/p65 decreased and nuclear NF-kappaB/p50 increased, associated with nuclear BCL-3 and a low level of TNF-alpha, indicating onset of spontaneous resolution. Treatment limited PKCzeta cleavage, with expression of nuclear NF-kappaB/p50 and BCL-3 and low nuclear NF-kappaB/p65 promoting macrophage survival, as evidenced by Bcl-2 expression. At 24 hours, intraocular treatment decreased membranous expression of PKCzeta by ocular cells, reduced vascular leakage with low nitric-oxide synthase-2 expression in vascular endothelial cells, and limited inflammatory cell infiltration with decreased intraocular TNF-alpha, interleukin-6, and nitric-oxide synthase-2 mRNA. Importantly, treatment decreased nuclear NF-kappaB/p65, increased transforming growth factor-beta2, and reduced caspase 3 expression in infiltrating macrophages, implying a change of their phenotype within ocular microenvironment. Treatment accelerated endotoxin-induced uveitis resolution through premature apoptosis of neutrophils related to high expression of toll-like receptor 4 and caspase 3.

Authors+Show Affiliations

INSERM U598, Centre Biomédical des Cordeliers, 15, rue de l'Ecole de Medecine 75270, Paris cedex 06, France. ydekozak@ccr.jussieu.frNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17392164

Citation

de Kozak, Yvonne, et al. "Protein Kinase Czeta (PKCzeta) Regulates Ocular Inflammation and Apoptosis in Endotoxin-induced Uveitis (EIU): Signaling Molecules Involved in EIU Resolution By PKCzeta Inhibitor and Interleukin-13." The American Journal of Pathology, vol. 170, no. 4, 2007, pp. 1241-57.
de Kozak Y, Omri B, Smith JR, et al. Protein kinase Czeta (PKCzeta) regulates ocular inflammation and apoptosis in endotoxin-induced uveitis (EIU): signaling molecules involved in EIU resolution by PKCzeta inhibitor and interleukin-13. Am J Pathol. 2007;170(4):1241-57.
de Kozak, Y., Omri, B., Smith, J. R., Naud, M. C., Thillaye-Goldenberg, B., & Crisanti, P. (2007). Protein kinase Czeta (PKCzeta) regulates ocular inflammation and apoptosis in endotoxin-induced uveitis (EIU): signaling molecules involved in EIU resolution by PKCzeta inhibitor and interleukin-13. The American Journal of Pathology, 170(4), 1241-57.
de Kozak Y, et al. Protein Kinase Czeta (PKCzeta) Regulates Ocular Inflammation and Apoptosis in Endotoxin-induced Uveitis (EIU): Signaling Molecules Involved in EIU Resolution By PKCzeta Inhibitor and Interleukin-13. Am J Pathol. 2007;170(4):1241-57. PubMed PMID: 17392164.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protein kinase Czeta (PKCzeta) regulates ocular inflammation and apoptosis in endotoxin-induced uveitis (EIU): signaling molecules involved in EIU resolution by PKCzeta inhibitor and interleukin-13. AU - de Kozak,Yvonne, AU - Omri,Boubaker, AU - Smith,Justine R, AU - Naud,Marie-Christine, AU - Thillaye-Goldenberg,Brigitte, AU - Crisanti,Patricia, PY - 2007/3/30/pubmed PY - 2007/5/5/medline PY - 2007/3/30/entrez SP - 1241 EP - 57 JF - The American journal of pathology JO - Am J Pathol VL - 170 IS - 4 N2 - We show that inhibitory effect of interleukin-13 on endotoxin-induced uveitis in the Lewis rat is dependent on signaling activity of protein kinase Czeta (PKCzeta). To understand the effect of interleukin-13 or PKCzeta inhibitor treatment, the activation status of rat bone marrow-derived macrophages was studied in vitro. At 6 hours, lipopolysaccharide-stimulated macrophages produced tumor necrosis factor-alpha (TNF-alpha) with nuclear factor kappaB (NF-kappaB)/p65 expression. Treatment led to absence of NF-kappaB/p65 expression and low levels of TNF-alpha, suggesting accelerated inactivation of macrophages. At 24 hours after lipopolysaccharide stimulation, nuclear NF-kappaB/p65 decreased and nuclear NF-kappaB/p50 increased, associated with nuclear BCL-3 and a low level of TNF-alpha, indicating onset of spontaneous resolution. Treatment limited PKCzeta cleavage, with expression of nuclear NF-kappaB/p50 and BCL-3 and low nuclear NF-kappaB/p65 promoting macrophage survival, as evidenced by Bcl-2 expression. At 24 hours, intraocular treatment decreased membranous expression of PKCzeta by ocular cells, reduced vascular leakage with low nitric-oxide synthase-2 expression in vascular endothelial cells, and limited inflammatory cell infiltration with decreased intraocular TNF-alpha, interleukin-6, and nitric-oxide synthase-2 mRNA. Importantly, treatment decreased nuclear NF-kappaB/p65, increased transforming growth factor-beta2, and reduced caspase 3 expression in infiltrating macrophages, implying a change of their phenotype within ocular microenvironment. Treatment accelerated endotoxin-induced uveitis resolution through premature apoptosis of neutrophils related to high expression of toll-like receptor 4 and caspase 3. SN - 0002-9440 UR - https://www.unboundmedicine.com/medline/citation/17392164/Protein_kinase_Czeta__PKCzeta__regulates_ocular_inflammation_and_apoptosis_in_endotoxin_induced_uveitis__EIU_:_signaling_molecules_involved_in_EIU_resolution_by_PKCzeta_inhibitor_and_interleukin_13_ DB - PRIME DP - Unbound Medicine ER -