Preferential promotion of apoptosis of monocytes by Lactobacillus casei rhamnosus soluble factors

Background & aims: inflammatory bowel disease (IBD) is characterized by dense infiltrates of and defective apoptosis by mucosal cell populations. Some probiotics inhibit monocytes' expansion, although mechanisms remain unknown. Supernatants of Lactobacillus strains were investigated for inducing apoptosis of monocytes. Methods: Secreted factors produced by Latobacillus strains were tested on human lymphocytes, monocytes and a human monocytic leukemia-cell line (THP-1). Cell death mechanisms were investigated by a variety of methods. Lipopolysaccharide (LPS)-induced proinflammatory cytokines (IL-1 beta, IL-6, IL-8, TNF-alpha) and anti-inflammatory TGF-beta 1 were determined. Results: Soluble factor(s) from Lactobacillus casei rhamnosus strain supernatants (LcrS) effectively induced apoptosis of immune cells. These were mainly soluble proteins (MW 5-30 kDa; LcrS(5-30)). For immune cells, but not human colonic epithelial carcinoma cells (HT-29), pretreatment with LcrS(5-30) significantly promoted apoptosis via a mitochondrial pathway. LcrS(5-30) suppressed pro-inflammatory cytokines and induced anti-inflammatory TGF-beta 1. Conclusions: Probiotic Lcr produced heat-stable molecules (MW range 5-30 kDa) that promoted immune cell apoptosis without affecting intestinal epithelial cells. LcrS(5-30) triggered apoptosis by a mitochondrial pathway, but not via TGF-beta signaling pathway. LcrS(5-30) also inhibited LPS-induced inflammatory cytokines by immune cells. Thus, LcrS(5-30) promotes apoptosis of immune cells, and suggests probiotics-based regimens for prevention of IBD. (C) 2009 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.