MEDAG UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
SLC7A11 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
SOD2 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
CHP2 DOWN in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
MAFF UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
LOX UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
ANGPTL4 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
GABPB1 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
ITGA2 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
LMCD1 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
AGPAT3 DOWN in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
IL6 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
DNAJB1 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
(Sample) stimulus/phorbol 12-myristate 13-acetate (PMA)/ionomycin (IO))
phorbol 12-myristate 13-acetate (PMA)/ionomycin (IO))
JMY UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
IL1RL1 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
IL6ST UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
INSIG1 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
SERPINE1 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
IL18R1 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
SEC24A UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
CXCL1 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
CREM UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
KLHL29 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
ZNF331 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
SLC2A3 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
Analysis of 'co-cultured with L. casei BL23' vs 'no co-culturing with probiotic bacteria' in 'fresh specimen; PMA/IO stimulation'
FERMT2 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
CD274 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
TAGAP UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
C5orf30 DOWN in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
ERN1 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
CCRN4L UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
ADAMTS9 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
G0S2 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
RRAD UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
TMEM158 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
RAB8B UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
PNPLA8 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
(Factor value) STIMULUS/phorbol 12-myristate 13-acetate (PMA)/ionomycin (IO))
ADM UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
(Sample) organism part/colonic intestinal mucosa
KCNE4 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
AP3S2 DOWN in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
(Factor value) GROWTH_CONDITION/co-cultured with L. casei BL23
SLC1A1 DOWN in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
THAP2 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
SLC35D1 DOWN in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
RORA UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
HOMER1 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
GADD45G UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
(Sample) growth condition/co-cultured with L. plantarum 299v
BIRC3 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
IL1B UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
HIVEP2 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
LIF UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
TFPI2 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
TM4SF1 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
GEM UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
NPC1 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
ZNF267 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
TMEM56 DOWN in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
CXCL11 DOWN in 'co-cultured with L. casei BL23' vs 'no co-culturing with probiotic bacteria' in 'fresh specimen; PMA/IO stimulation'
UBE2H UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
PAQR8 DOWN in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
TUBAL3 DOWN in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
TNFAIP6 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
PTX3 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
ANKRD9 DOWN in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
BASP1 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
RLF UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
NAPEPLD DOWN in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
NFIL3 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
CDS1 DOWN in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
CXCL2 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
CTSL UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
THBS1 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
CXCL8 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
(Sample) growth condition/co-cultured with L. plantarum 299v (A-)
HSPH1 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
Background: In the last decade, much attention has been drawn to probiotic bacteria in the context of inflammatory bowel disease (IBD), since the potential of certain strains to attenuate inflammation was demonstrated in several animal experiments and clinical studies. Data in humans elucidating the molecular mechanism of probiotic action are still scarce. To this end, we used an organ culture system of human colon mucosa and investigated the gene expression profiles after treatment with different probiotic bacteria in phorbol 12-myristate 13-acetate (PMA)/ionomycin (IO)) stimulated samples using whole genome microarrays. Moreover, we analyzed changes occurring in the intestinal explants cultured for 8 hours when compared to fresh, directly frozen mucosa, in order to infer the suitability of the system to study an inflammatory stimulus and likely antiinflammatory responses. Results: Culturing intestinal colon fragments during 8 hours elicited differential gene expression in 283 genes, 229 upregulated and 54 downregulated. Upregulated genes were predominantly related to apoptosis, whereas downregulated genes encoded mitochondrial proteins. No specific enrichment of genes related to inflammation or immune response could be detected, confirming the suitability of the system to further study the inmunomodulatory/anti-inflammatory properties of Lactobacillus casei BL23 (BL23), L.plantarum 299v (LP299v) and L.plantarum 299v (A-) (LP299v (A-)), a mutant strain with reduced adhesive properties to enterocytes. Intestinal explants were stimulated with PMA/IO for 3 hours and subsequently incubated with probiotic bacteria for 4 h. ANOVA analysis (p âÂÂ¤ 0,01) revealed 205 differentially expressed genes between Control, PMA/IO (Inflamed), and the 3 bacterial treatments. Most importantly, a number of PMA/IO induced genes related to immune response and immune system process such as IL-2, IFN-ÃÂ³, IL17A and pro-inflammatory cytokines CXCL9 and CXCL11 were downregulated by BL23, LP299v and LP299v (A-). The behaviour of the three Lactobacillus strains was quite similar, although their presence induced differential expression of a small number of genes in a strain dependent manner. Conclusion: The human colon organ culture was found to be a suitable model for the study of inflammatory/anti-inflammatory stimuli, and therefore it constitutes a valuable tool to determine the inmunomodulatory effect of probiotic bacteria. The global transcriptional profile evoked by strains BL23, LP299v and LP299v (A-) in artificially inflamed tissue indicated a clear homeostasis restoring effect, including a decrease of the signals produced by activated T cells. Macroscopically healthy colonic intestinal tissue was obtained at surgery from 3 patients. Intestinal explants were treated with PMA and ionomycin for 3 h to induce pro-inflammatory conditions. Then, culture medium was changed and replaced with either medium or medium containing either Lactobacillus casei BL23, Lactobacillus plantarum 299v, or a nonadherent mutant of L. plantarum 299v (A-) and incubated for further 4 hours. In parallel, control intestinal explants were cultured without any treatment of PMA/ionomycin or probiotic bacteria and compared to directly frozen tissue in order to evaluate changes in gene expression which are due solely to the culture conditions.
MMP10 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
CLMP UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
IRAK2 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
MOGAT2 DOWN in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
IL1RN UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
NR4A3 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
BCL6 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
XRN1 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
PLAU UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
PRR15 DOWN in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
MMP1 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
RP11-30P6.6 DOWN in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
BCL2L11 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
SHROOM3 DOWN in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
DUSP4 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
DST UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
BHLHE40 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
(Factor value) SPECIMEN_WITH_KNOWN_STORAGE_STATE/frozen specimen
CPT2 DOWN in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
PFKFB3 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
HILPDA UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
CXCL3 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
CYP3A5 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
BRI3BP DOWN in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
(Sample) specimen with known storage state/fresh specimen
STC1 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
LRRC66 DOWN in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
PMAIP1 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
CD44 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
PITPNC1 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
RIPK2 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
CASC7 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
FLT1 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
TWIST1 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
CD83 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
ADRA2A DOWN in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
KRCC1 DOWN in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
CLEC2D UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
CFTR DOWN in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
XK DOWN in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
INHBA UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
AKR1C3 DOWN in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
GGT6 DOWN in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
ICOS UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
PDLIM4 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
ANGPT2 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
PBX4 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
(Factor value) GROWTH_CONDITION/co-cultured with L. plantarum 299v (A-)
MSMO1 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
EPB41L4B DOWN in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
SLC35G1 DOWN in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
(Sample) growth condition/co-cultured with L. casei BL23
(Factor value) SPECIMEN_WITH_KNOWN_STORAGE_STATE/fresh specimen
IGSF3 DOWN in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
SELE UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
(Sample) specimen with known storage state/frozen specimen
DUSP5 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
VAV3 DOWN in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
(Factor value) GROWTH_CONDITION/co-cultured with L. plantarum 299v
DHRS11 DOWN in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
STAT4 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
SGMS2 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
DNAJA4 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
PANK1 DOWN in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
HGF UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
GCNT2 DOWN in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
VEGFA UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
GJC1 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
FGF2 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
CD55 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
TRIM36 DOWN in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
BTG2 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
FAM49A UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
PTGS2 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
GLS UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
ANKRD37 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
TMEM54 DOWN in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
CEMIP UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
DDIT4 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
(Factor value) GROWTH_CONDITION/no co-culturing with probiotic bacteria
DUSP2 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
IL7R UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
MMP3 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
CXCL11 DOWN in 'co-cultured with L. plantarum 299v' vs 'no co-culturing with probiotic bacteria' in 'fresh specimen; PMA/IO stimulation'
ZFAND5 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
SYTL3 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
IL13RA2 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
ERO1L UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
BAG3 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
Analysis of 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
LY9 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
CORO2A DOWN in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
LDLR UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
PNP UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
BCL2A1 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
IFRD1 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
REL UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
FUCA1 DOWN in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
ICAM1 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
NKX3-1 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
TACSTD2 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
IL1A UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
CXCL6 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
(Sample) growth condition/no co-culturing with probiotic bacteria
SLC26A2 DOWN in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
EPHA2 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
SERPINB2 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
ITPRIP UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
CMTM4 DOWN in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
TSLP UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
PLAUR UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
NHSL1 DOWN in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
IDO1 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
PDPN UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
CCL4 UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
WSCD1 DOWN in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
ARL5B UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'
Analysis of 'co-cultured with L. plantarum 299v' vs 'no co-culturing with probiotic bacteria' in 'fresh specimen; PMA/IO stimulation'
C2CD4A UP in 'frozen specimen' vs 'fresh specimen' in 'no probiotics; no stimulation'