Regulation of CD93 Cell Surface Expression by Protein Kinase C Isoenzymes

Ikewaki, Nobunao; Kulski, Jerzy K.; Inoko, Hidetoshi

doi:10.1111/j.1348-0421.2006.tb03774.x

Cited by 14 publications

(15 citation statements)

References 41 publications

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“…Despite its membrane-bound form, CD93 might be shed from the cell surface upon cellular activation (26,47,48). A similar ectodomain release has been reported for L-selectin and CD44, as well as for TNF-a and other cytokines (35).…”

Section: Discussionsupporting

confidence: 60%

CD93/AA4.1: A Novel Regulator of Inflammation in Murine Focal Cerebral Ischemia

Harhausen¹,

Prinz²,

Ziegler

et al. 2010

The Journal of Immunology

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International audienceThe stem-cell marker CD93 (AA4.1/C1qRp) has been described as a potential complement C1q-receptor. Its exact molecular function, however, remains unknown. By using global expression profiling we showed that CD93-mRNA is highly induced after transient focal cerebral ischemia. CD93 protein is upregulated in endothelial cells, but also in selected macrophages and microglia. To elucidate the potential functional role of CD93 in postischemic brain damage, we used mice with a targeted deletion of the CD93 gene. After 30 min of occlusion of the middle cerebral artery and 3 d of reperfusion these mice displayed increased leukocyte infiltration into the brain, increased edema, and significantly larger infarct volumes (60.8 ± 52.2 versus 23.9 ± 16.6 mm3) when compared with wild-type (WT) mice. When the MCA was occluded for 60 min, after 2 d of reperfusion the CD93 knockout mice still showed more leukocytes in the brain, but the infarct volumes were not different from those seen in WT animals. To further explore CD93-dependent signaling pathways, we determined global transcription profiles and compared CD93-deficient and WT mice at various time points after induction of focal cerebral ischemia. We found a highly significant upregulation of the chemokine CCL21/Exodus-2 in untreated and treated CD93-deficient mice at all time points. Induction of CCL21 mRNA and protein was confirmed by PCR and immunohistochemistry. CCL21, which was formerly shown to be released by damaged neurons and to activate microglia, contributes to neurodegeneration. Thus, we speculate that CD93-neuroprotection is mediated via suppression of the neuroinflammatory response through downregulation of CCL21

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Section: Discussionsupporting

confidence: 60%

CD93/AA4.1: A Novel Regulator of Inflammation in Murine Focal Cerebral Ischemia

Harhausen¹,

Prinz²,

Ziegler

et al. 2010

The Journal of Immunology

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“…The third overexpressed gene in Table 3, CD93 / Cq1R also represents a cell surface protein present in the myeloid lineage with no previous association with epithelial cells 18. It has been identified as a marker for myeloid and hepatic-yielding stem cells 19.…”

Section: Resultsmentioning

confidence: 99%

Molecular Profiling of Conjunctival Epithelial Side-Population Stem Cells: Atypical Cell Surface Markers and Sources of a Slow-Cycling Phenotype

Akıncı¹,

Turner²,

Taveras³

et al. 2009

Invest. Ophthalmol. Vis. Sci.

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PURPOSE Side-population (SP) cells isolated from limbal and conjunctival epithelia derive from cells that are slow cycling in vivo, a known feature of tissue stem cells. The purpose of this study was to define the molecular signature of the conjunctival SP cells and identify markers and signaling pathways associated with the phenotype of these cells. METHODS Overnight cultures of freshly isolated human conjunctival epithelial cells stained with Hoechst 33342 were sorted by flow cytometry into SP and non-SP cohorts. Isolated RNA was processed for microarray analysis using a commercial oligonucleotide spotted array. Results were validated at the gene and protein levels by quantitative PCR and immunologic methods. Data mining methods were used to identify cellular processes relevant for stem cell function. RESULTS Comparative analyses of transcripts expression based on present and absent software calls across four replicate experiments identified 16,993 conjunctival epithelial transcripts including 10,266 unique known genes of ~24,000 represented in the array. Of those genes, 1254 and 363 were overexpressed (>2-fold) or underexpressed (<0.5-fold), respectively, in the SP. The overexpressed set included genes coding for proteins that have been associated with (1) embryonic development and/or stem cell self renewal (MSX, MEIS, ID, Hes1, and SIX homeodomain genes); (2) cell survival (e.g., CYP1A1 to degrade aromatic genotoxic compounds); (3) cycling rate (e.g., DUSPs and Pax6 to foster slow cycling); and (4) genes whose expression is not typical in epithelia (e.g., CD62E). CONCLUSIONS The molecular signature of conjunctival SP cells is consistent with a stem cell phenotype. Their gene expression patterns underpin slow cycling and plasticity, features associated with tissue stem cells. The results provide valuable insights for the preservation and/or expansion of epithelial stem cells.

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“…3). The strongest inhibitory effect on IL-8 production was obtained with Rottlerin, which exerts an inhibitory effect against the PKC delta isoenzyme and can directly regulate several biological phenomena, including cytokine production, cell adhesion/aggregation, and cell apoptosis (26,28,33).…”

Section: Immunological Actions Of Sophy β-Glucanmentioning

confidence: 99%

Immunological Actions of Sophy β‐Glucan (β‐1,3‐1,6 Glucan), Currently Available Commercially as a Health Food Supplement

Ikewaki

Fujii²,

Onaka³

et al. 2007

Microbiology and Immunology

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-4). In these blocking experiments using the mAbs, the main differences in the results between PBMCs and U937 cells were that the mAbs against TLR-2 and TLR-4 did not block the Sophy ␤-glucan-induced production of IL-8 in the U937 cells. Furthermore, a mAb to the ␤-glucan receptor, Dectin-1, significantly (P<0.05) blocked the Sophy ␤-glucaninduced DNA synthesis in the PBMCs, and Sophy ␤-glucan-induced production of IL-8 in the U937 cells. The Sophy ␤-glucan-induced production of IL-8 in the U937 cells was significantly (P<0.01) blocked by the conventional protein kinase C (PKC) inhibitor Go6976, the novel PKC inhibitor Rottlerin, the protein kinase A (PKA) inhibitor H-89, and the protein tyrosine kinase (PTK) inhibitor herbimycin A. Among these, the blocking effect of the novel PKC (PKC delta isoenzyme) inhibitor Rottlerin was the most pronounced. Studies employing reverse transcriptase-polymerase chain reaction (RT-PCR) showed that Sophy ␤-glucan stimulated the expression of IL-8 mRNA in the U937 cells, and that this induction was inhibited by Rottlerin. Sophy ␤-glucan also blocked the stimulator cell induction of DNA synthesis and IFN-␥ production in the responder cells in a one-way mixed lymphocyte reaction (MLR) using allogenic PBMCs. Interestingly, immunoglobulin G (IgG), but not IgM to Sophy ␤-glucan was detected in the sera derived from normal adult donors and from the umbilical cord blood of neonates. Taken together, these findings strongly suggest that the Sophy ␤-glucan may have unique immune regulatory or enhancing properties that could be exploited by the health food, medical and pharmaceutical industries.

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Regulation of CD93 Cell Surface Expression by Protein Kinase C Isoenzymes

Cited by 14 publications

References 41 publications

CD93/AA4.1: A Novel Regulator of Inflammation in Murine Focal Cerebral Ischemia

CD93/AA4.1: A Novel Regulator of Inflammation in Murine Focal Cerebral Ischemia

Molecular Profiling of Conjunctival Epithelial Side-Population Stem Cells: Atypical Cell Surface Markers and Sources of a Slow-Cycling Phenotype

Immunological Actions of Sophy β‐Glucan (β‐1,3‐1,6 Glucan), Currently Available Commercially as a Health Food Supplement

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