Bucillamine inhibits CD40-mediated Akt activation and antibody production in mouse B-cell lymphoma.

The improvement of rheumatoid factor titers in patients with rheumatoid arthritis is one of the significant clinical effects of bucillamine (Buc). In this study, we investigated the effects of SA981, an active metabolite of Buc, and methotrexate (MTX) on CD40-mediated antibody production using mouse B-cell lymphoma, BCL1. SA981 significantly attenuated CD40-mediated antibody production in a concentration-dependent manner, but weakly affected cell proliferation. In contrast, MTX did not attenuate CD40-mediated antibody production until it had strongly inhibited cell proliferation at a concentration of 100 nM. CD40 signaling induced protein phosphorylation, including Akt phosphorylation, p38 mitogen-activated protein kinase (p38MAPK), and IκBα. SA981 at a concentration of 30 μM attenuated CD40-mediated Akt phosphorylation, but not p38MAPK or IκBα phosphorylation. MTX at a concentration of 100 nM did not affect CD40-mediated Akt, p38MAPK, or IκBα phosphorylation. Commercially available Akt inhibitor VIII significantly attenuated CD40-mediated IgM production at a concentration of 100 nM without significant inhibition of cell proliferation. These results suggest that SA981 inhibits CD40-mediated antibody production in mouse B-cell lymphoma, at least in part, by attenuation of Akt phosphorylation.
AuthorsFumio Tsuji, Chikako Setoguchi, Masahiro Okamoto, Iwao Seki, Minoru Sasano, Hiroyuki Aono
JournalInternational immunopharmacology (Int Immunopharmacol) Vol. 14 Issue 1 Pg. 47-53 (Sep 2012) ISSN: 1878-1705 [Electronic] Netherlands
PMID22735757 (Publication Type: Journal Article)
CopyrightCopyright © 2012 Elsevier B.V. All rights reserved.
Chemical References
  • Antigens, CD40
  • bucillamine disulfide
  • Oncogene Protein v-akt
  • Cysteine
  • bucillamine
  • Methotrexate
  • Animals
  • Antibody Formation (drug effects)
  • Antigens, CD40 (immunology)
  • Cell Line, Tumor
  • Cell Proliferation (drug effects)
  • Cysteine (administration & dosage, analogs & derivatives, chemistry)
  • Enzyme Activation (drug effects, immunology)
  • Methotrexate (administration & dosage)
  • Mice
  • Oncogene Protein v-akt (metabolism)
  • Phosphorylation (drug effects, immunology)

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