Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The B cell line, MRL159.5, was established by somatic hybridization between splenic MRL/MP-lpr/lpr (lpr) mice B cells and 2.52M, a hypoxanthine-aminopterine-thymidine (HAT) medium-sensitive B cell line mutant. It possessed a receptor molecule for mouse erythrocytes treated with bromelain (Br-MRBC) on its surface, likely to be an autoreactive B cell clone specific for Br-MRBC as detected by rosette-forming assay with Br-MRBC. MRL159.5 spontaneously produced IL-6 and secreted IgM, and was induced to augment IgM secretion when treated with Br-MRBC or IL-6. Triggering of CD40 led to an augmentation of IgM secretion as well as IL-6 expression. Blocking the binding of IL-6 to its cellular receptor through the use of inhibitory antibodies inhibited CD40-induced IgM secretion, suggesting a possible autocrine role of IL-6 for CD40-induced differentiation of this B cell hybridoma. Addition of IL-4 or Br-MRBC augmented IL-6 expression as well as IgM secretion by CD40-activated MRL159.5 cells. CD40 also augmented tumour necrosis factor-alpha (TNF-alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF) expression but resulted in decreased IL-10 expression. Furthermore, under conditions where IL-6 expression was augmented, IL-6R alpha (gp80) expression was down-regulated, suggesting a negative feedback mechanism of an IL-6 autocrine loop in this hybridoma. These results demonstrate a role by which T cell-dependent activation through CD40 regulates an IL-6 autocrine loop, controlling differentiation of autoreactive B cells in autoimmune disease.
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PMID:Regulation of cytokine expression by an autoreactive B cell clone derived from MRL/MP-lpr/lpr mice. 976 95

Oral bromelain has been anecdotally reported to decrease inflammation in ulcerative colitis (UC). Proteolytically active bromelain is known to decrease expression of mRNAs encoding pro-inflammatory cytokines by human leukocytes in vitro. To assess the effect of bromelain on mucosal secretion of cytokines in inflammatory bowel disease (IBD), endoscopic colon biopsies from patients with UC, Crohn's disease (CD), and non-IBD controls were treated in vitro with bromelain or media, then cultured. Secretion of pro-inflammatory cytokines and chemokines was measured. Significant increases in granulocyte colony-stimulating factor (G-CSF), interferon (IFN)-gamma, interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF) were detected in the media from actively inflamed areas in UC and CD as compared with non-inflamed IBD tissue and non-IBD controls. In vitro bromelain treatment decreased secretion of G-CSF, granulocyte-macrophage colony-stimulating factor (GM-CSF), IFN-gamma, CCL4/macrophage inhibitory protein (MIP)-1beta, and TNF by inflamed tissue in IBD. Bromelain may be a novel therapy for IBD.
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PMID:Bromelain treatment decreases secretion of pro-inflammatory cytokines and chemokines by colon biopsies in vitro. 1816 Mar 45