title: Effects of sotrastaurin, mycophenolic acid and everolimus on human B-lymphocyte function and activation.
abstract: Humoral rejection processes may lead to allograft injury and subsequent dysfunction. Today, only one B-cell-specific agent is in clinical use and the effects of standard and new immunosuppressant substances on B-cell activation and function are not fully clarified. The impact of sotrastaurin, mycophenolic acid and everolimus on human B-lymphocyte function was assessed by analysing proliferation, apoptosis, CD80/CD86 expression and immunoglobulin and IL-10 production in primary stimulated B cells. In addition, B-cell co-cultures with pre-activated T cells were performed to evaluate the effect of the different immunosuppressive agents on T-cell-dependent immunoglobulin production. Sotrastaurin did not inhibit B-cell proliferation, CD80/CD86 expression, and IgG production and had only minor effects on IgM levels at the highest concentration administered. In contrast, mycophenolic acid and everolimus had strong effects on all B-cell functions in a dose-dependent manner. All immunosuppressive agents caused decreased immunoglobulin levels in T-cell-dependent B-cell cultures. The data provided here suggest that mycophenolic acid and everolimus, but not sotrastaurin, are potent inhibitors of human B-lymphocyte function and activation.
authors: Department of Nephrology, Universitätsmedizin Charité Campus Mitte, Berlin, Germany. mareen.matz@charite.de
authors: Mareen
authors: M
authors: Matz
authors: Martin
authors: M
authors: Lehnert
authors: Christine
authors: C
authors: Lorkowski
authors: Katharina
authors: K
authors: Fabritius
authors: Nadine
authors: N
authors: Unterwalder
authors: Salim
authors: S
authors: Doueiri
authors: Ulrike A
authors: UA
authors: Weber
authors: Mir-Farzin
authors: MF
authors: Mashreghi
authors: Hans-H
authors: HH
authors: Neumayer
authors: Klemens
authors: K
authors: Budde
mesh_terms: D017209:Apoptosis; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D018122:B7-1 Antigen / Q000096:biosynthesis; D051940:B7-2 Antigen / Q000096:biosynthesis; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000068338:Everolimus; D006084:Graft Rejection; D006801:Humans; D056724:Immunity, Humoral; D007074:Immunoglobulin G / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D007136:Immunoglobulins / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D016753:Interleukin-10 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology; D009173:Mycophenolic Acid / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014184:Transplantation, Homologous
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; D004791:Enzyme Inhibitors; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007136:Immunoglobulins; D007166:Immunosuppressive Agents; D011758:Pyrroles; D011799:Quinazolines; D016753:Interleukin-10; C543528:sotrastaurin; D000068338:Everolimus; D009173:Mycophenolic Acid; D020123:Sirolimus