Preferential promotion of apoptosis of monocytes by Lactobacillus casei rhamnosus soluble factors.
OBJECTIVE
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 Lactobacillus 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-1beta, IL-6, IL-8, TNF-alpha) and anti-inflammatory TGF-beta1 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-beta1.


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.
Chiu
Yi-Han
YH
Department of Biological Science and Technology, National Chiao Tung University, Hsin Chu 30068, Taiwan.
Hsieh
Yi-Jen
YJ
Liao
Kuang-Wen
KW
Peng
Kou-Cheng
KC
D000704:Analysis of Variance; D017209:Apoptosis / Q000187:drug effects*; D001426:Bacterial Proteins / Q000276:immunology* / Q000494:pharmacology; D015153:Blotting, Western; D018929:Cell Culture Techniques; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology; D006801:Humans; D020287:In Situ Nick-End Labeling; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology; D007780:Lacticaseibacillus casei / Q000276:immunology*; D052201:Lacticaseibacillus rhamnosus / Q000276:immunology*; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D001426:Bacterial Proteins; D016207:Cytokines