Nicotinamide inhibits B lymphocyte activation by disrupting MAPK signal transduction.
Nicotinamide (NAm) represents both a pharmacological agent known to express cell preserving and anti-inflammatory properties, and a useful investigational tool to elucidate cellular pathways regulating a wide range of cellular functions. We demonstrate in this study that exogenous NAm, when used at pharmacological doses, inhibits activation of primary murine B lymphocytes in response to multiple ligands. NAm appears to affect a membrane proximal event leading to MAPKs activation, a transduction pathway shared by multiple receptors including the antigen-specific B cell receptor, CD38, CD40 and TLR4 receptors. NAm inhibited phospho-ERK accumulation, and only marginally affected phospho-p38 and phospho-JNK induction upon BCR stimulation of naive B lymphocytes. Accordingly, NAm also affected the expression of known targets of the MAPK ERK pathway such as CD69 and cyclin D2. Based on a comparison with well-characterized pharmacological inhibitors, we suggest in this work that NAm may inhibit a post-translational modification mediated by a yet unidentified mono(ADP-ribose)transferase. Collectively, our observations indicate that in addition to its previously described effect on cells of the innate immune system, NAm is able to modulate the activity of B lymphocytes suggesting a potential role of this vitamin in regulating antibody-mediated autoimmune disorders.
Daniel
Julien
J
Laboratoire de Physiologie Animale, Institut de Biologie et Médecine Moléculaire IBMM, Faculté des Sciences, Université Libre de Bruxelles, Belgium.
Marechal
Yoann
Y
Van Gool
Frédéric
F
Andris
Fabienne
F
Leo
Oberdan
O
D019797:3-Iodobenzylguanidine / Q000494:pharmacology; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D005260:Female; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000187:drug effects*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D009536:Niacinamide / Q000494:pharmacology*; D011947:Receptors, Antigen, B-Cell; D000099192:CD69 Antigens
D019797:3-Iodobenzylguanidine; D000246:Adenosine Diphosphate Ribose; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D002118:Calcium; D037181:Lectins, C-Type; D009536:Niacinamide; D011947:Receptors, Antigen, B-Cell; D000099192:CD69 Antigens