Renal and Hematological Effects of CLCF-1, a B-Cell-Stimulating Cytokine of the IL-6 Family
CLCF-1 is a cytokine known for B-cell stimulation and for neurotrophic properties. We have identified CLCF-1 as a potential injurious factor in the human renal disease focal segmental glomerulosclerosis (FSGS). We investigated its effects on renal cells and renal function in in vitro and in vivo stu...
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2015/714964 |
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| author | Virginia J. Savin Mukut Sharma Jianping Zhou David Gennochi Timothy Fields Ram Sharma Ellen T. McCarthy Tarak Srivastava Jos Domen Aurélie Tormo Jean-François Gauchat |
| author_facet | Virginia J. Savin Mukut Sharma Jianping Zhou David Gennochi Timothy Fields Ram Sharma Ellen T. McCarthy Tarak Srivastava Jos Domen Aurélie Tormo Jean-François Gauchat |
| author_sort | Virginia J. Savin |
| collection | DOAJ |
| description | CLCF-1 is a cytokine known for B-cell stimulation and for neurotrophic properties. We have identified CLCF-1 as a potential injurious factor in the human renal disease focal segmental glomerulosclerosis (FSGS). We investigated its effects on renal cells and renal function in in vitro and in vivo studies. Methods include measurement of the effect of CLCF-1 on phosphorylation of target molecules of the JAK/STAT pathway, on cytoskeleton and cell morphology in cultured podocytes, on albumin permeability of isolated rat glomeruli, and on tissue phosphorylation and urine albumin after acute or chronic CLCF-1 injection. In addition, cell sorting was performed to determine the presence of cells expressing CLCF-1 in spleen and bone marrow of normal mice and the effect of CLCF-1 infusion on splenic B-cell populations. CLCF-1 increased phosphorylation of STAT3 in multiple cell types, activated podocytes leading to formation of lamellipodia and decrease in basal stress fibers, increased glomerular albumin permeability, and increased STAT3 phosphorylation of peripheral blood cells and renal cortex. CLCF-1 increased urine albumin/creatinine ratio in mice and increased B-cell expression of IgG in mouse spleen. We conclude that CLCF-1 has potentially important systemic effects, alters podocyte function, and may contribute to renal dysfunction and albuminuria. |
| format | Article |
| id | doaj-art-b2323fe2846045589d7bc655d492f790 |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-b2323fe2846045589d7bc655d492f7902025-02-03T06:13:11ZengWileyJournal of Immunology Research2314-88612314-71562015-01-01201510.1155/2015/714964714964Renal and Hematological Effects of CLCF-1, a B-Cell-Stimulating Cytokine of the IL-6 FamilyVirginia J. Savin0Mukut Sharma1Jianping Zhou2David Gennochi3Timothy Fields4Ram Sharma5Ellen T. McCarthy6Tarak Srivastava7Jos Domen8Aurélie Tormo9Jean-François Gauchat10Renal Research Laboratory, Research and Development, MBRF and Kansas City VA Medical Center, Kansas City, MO 64128, USARenal Research Laboratory, Research and Development, MBRF and Kansas City VA Medical Center, Kansas City, MO 64128, USARenal Research Laboratory, Research and Development, MBRF and Kansas City VA Medical Center, Kansas City, MO 64128, USARenal Research Laboratory, Research and Development, MBRF and Kansas City VA Medical Center, Kansas City, MO 64128, USAKidney Institute, University of Kansas Medical Center, Kansas City, KS 66160, USARenal Research Laboratory, Research and Development, MBRF and Kansas City VA Medical Center, Kansas City, MO 64128, USAKidney Institute, University of Kansas Medical Center, Kansas City, KS 66160, USARenal Research Laboratory, Research and Development, MBRF and Kansas City VA Medical Center, Kansas City, MO 64128, USASection of Cardiac Surgery, Children’s Mercy Hospital and University of Missouri at Kansas City, Kansas City, MO 64108, USADepartment of Pharmacology, University of Montreal, Montreal, QC, H3T 1J4, CanadaDepartment of Pharmacology, University of Montreal, Montreal, QC, H3T 1J4, CanadaCLCF-1 is a cytokine known for B-cell stimulation and for neurotrophic properties. We have identified CLCF-1 as a potential injurious factor in the human renal disease focal segmental glomerulosclerosis (FSGS). We investigated its effects on renal cells and renal function in in vitro and in vivo studies. Methods include measurement of the effect of CLCF-1 on phosphorylation of target molecules of the JAK/STAT pathway, on cytoskeleton and cell morphology in cultured podocytes, on albumin permeability of isolated rat glomeruli, and on tissue phosphorylation and urine albumin after acute or chronic CLCF-1 injection. In addition, cell sorting was performed to determine the presence of cells expressing CLCF-1 in spleen and bone marrow of normal mice and the effect of CLCF-1 infusion on splenic B-cell populations. CLCF-1 increased phosphorylation of STAT3 in multiple cell types, activated podocytes leading to formation of lamellipodia and decrease in basal stress fibers, increased glomerular albumin permeability, and increased STAT3 phosphorylation of peripheral blood cells and renal cortex. CLCF-1 increased urine albumin/creatinine ratio in mice and increased B-cell expression of IgG in mouse spleen. We conclude that CLCF-1 has potentially important systemic effects, alters podocyte function, and may contribute to renal dysfunction and albuminuria.http://dx.doi.org/10.1155/2015/714964 |
| spellingShingle | Virginia J. Savin Mukut Sharma Jianping Zhou David Gennochi Timothy Fields Ram Sharma Ellen T. McCarthy Tarak Srivastava Jos Domen Aurélie Tormo Jean-François Gauchat Renal and Hematological Effects of CLCF-1, a B-Cell-Stimulating Cytokine of the IL-6 Family Journal of Immunology Research |
| title | Renal and Hematological Effects of CLCF-1, a B-Cell-Stimulating Cytokine of the IL-6 Family |
| title_full | Renal and Hematological Effects of CLCF-1, a B-Cell-Stimulating Cytokine of the IL-6 Family |
| title_fullStr | Renal and Hematological Effects of CLCF-1, a B-Cell-Stimulating Cytokine of the IL-6 Family |
| title_full_unstemmed | Renal and Hematological Effects of CLCF-1, a B-Cell-Stimulating Cytokine of the IL-6 Family |
| title_short | Renal and Hematological Effects of CLCF-1, a B-Cell-Stimulating Cytokine of the IL-6 Family |
| title_sort | renal and hematological effects of clcf 1 a b cell stimulating cytokine of the il 6 family |
| url | http://dx.doi.org/10.1155/2015/714964 |
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