Continuous activation of the immune system inside a tissue can lead to remodelling of the tissue structure and creation of a specific microenvironment, such as during the tumour development. Chronic inflammation is a central player in stimulating changes that alter the tissue stroma and can lead to fibrotic evolution. In the colon mucosa, regulatory mechanisms, including TGF-β1, avoid damaging inflammation in front of the continuous challenge by the intestinal microbiome. Inducing either DSS colitis or AOM colorectal carcinogenesis in AVN-Wistar rats, we evaluated at one month after the end of each treatment whether immunological changes and remodelling of the collagen scaffold were already in development. At this time point, we found in both models a general downregulation of pro-inflammatory cytokines and even of TGF-β1, but not of IL-6. Moreover, we demonstrated by multi-photon microscopy the simultaneously presence of pro-fibrotic remodelling of the collagen scaffold, with measurable changes in comparison to the control mucosa. The scaffold was significantly modified depending on the type of induced stimulation. These results suggest that at one month after the end of the DSS or AOM inductions, a smouldering inflammation is present in both induced conditions, since the pro-inflammatory cytokines still exceed, in proportion, the local homeostatic regulation of which TGF-β1 is a part (inflammatory threshold). Such an inflammation appears sufficient to sustain remodelling of the collagen scaffold that may be taken as a possible pathological marker for revealing pre-neoplastic inflammation.

• Keywords
• AOM, DSS-induced colitis, IL-6, chronic inflammation, collagen, colorectal cancer, tissue scaffold, tumour niche,
• Publication type
• Journal Article MeSH

The effect of nonpathogenic G+ bacterium B. firmus (BF) on stimulation of mouse peritoneal cells in vitro was evaluated by testing nitric-oxide-synthesis induction and cytokine formation. The reactivity was compared of peritoneal cells from two inbred mouse strains, C57B1/6 and BALB/c, which differ in their immunological reactivity. Peritoneal macrophages from C57B1/6 produced more nitric oxide after a 1-d cultivation with inactivated BF than those of BALB/c mice. In both strains, production can be further increased by adding exogenous IFN-gamma to the culture. There were no significant differences between peritoneal cells of these two mouse strains in cytokine production after optimal in vitro stimulation with BF. BF effectively activated peritoneal cells for the production of TNF-alpha, IL-1beta and IL-10, delipidated bacterium (DBF) being more efficient than BF in induction of IL-10 and TNF-alpha. On the other hand, BF had only small effect on IFN-gamma production and no detectable effect on IL-12 production. Macrophage activation by BF/DBF can represent one of the mechanisms responsible for previously described immunomodulatory activity of BF.

• MeSH
• Macrophage Activation * MeSH
• Bacillus immunology   MeSH
• Cell Culture Techniques methods   MeSH
• Cytokines immunology   metabolism   MeSH
• Lipopolysaccharides pharmacology   MeSH
• Mice, Inbred BALB C MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Organic Chemicals pharmacology   MeSH
• Nitric Oxide metabolism   MeSH
• Peritoneal Cavity cytology   MeSH
• Immunity, Innate MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Comparative Study MeSH
• Names of Substances
• Cytokines MeSH
• Lipopolysaccharides MeSH
• Nocardia delipidated cell mitogen MeSH Browser
• Organic Chemicals MeSH
• Nitric Oxide MeSH

Inactivated Bacillus firmus (BF), G+ nonpathogenic bacterium of the external environment, was coupled to ovalbumin (OVA) and used in immunization experiments as antigen carrier. Balb/c mice were immunized thrice intra-tracheally and intra-nasally with conjugates of OVA and BF. Surprisingly, administration of OVA-BF conjugates inhibited anti-OVA IgG response in both sera and mucosal secretions if compared to an exposure to OVA alone. The suppression of antigen-specific antibody production was accompanied by promotion of TH1 phenotype.

• MeSH
• Lymphocyte Activation MeSH
• Antigens administration & dosage   MeSH
• Administration, Intranasal MeSH
• Bacillus immunology   MeSH
• Immunization MeSH
• Immunoglobulin G biosynthesis   blood   MeSH
• Mice, Inbred BALB C MeSH
• Mice MeSH
• Drug Carriers MeSH
• Ovalbumin administration & dosage   immunology   MeSH
• Antibodies, Bacterial biosynthesis   blood   MeSH
• Immunity, Mucosal MeSH
• In Vitro Techniques MeSH
• Th1 Cells immunology   MeSH
• Trachea MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Antigens MeSH
• Immunoglobulin G MeSH
• Drug Carriers MeSH
• Ovalbumin MeSH
• Antibodies, Bacterial MeSH

A nonpathogenic bacterium of external environment possessing remarkable immunomodulatory activity, Bacillus firmus (BF) inactivated with formaldehyde, was given intragastrically to two genetically different mouse strains BALB/c (H-2d) and B10.BR/SnPh (B10.BR, H-2k) reared in conventional (CV) and B10.BR strain also in germ-free (GF) conditions. Repeated intragastric administration of BF (500 micrograms every other day over two weeks, starting at the age of 3 months) significantly enhanced intestinal IgA levels in CV BALB/c mice but did not affect intestinal IgA in CV B10.BR mice. In GF B10.BR mice, IgG levels in sera and intestinal washings increased after BF administration compared to CV B10.BR mice. In CV BALB/c mice, specific activity of enterocyte brush-border enzymes (lactase, gamma-glutamyltransferase, alkaline phosphatase) decreased after BF treatment; sucrase (sucrose alpha-glucosidase) activity was not affected. On the other hand, in B10.BR mice, specific activity of gamma-glutamyltransferase and dipeptidyl peptidase IV were higher after administration of BF in both CV and GF groups relative to untreated controls. The activities of lactase and glucoamylase (glucan 1,4-alpha-glucosidase) were significantly stimulated only in the group of GF B10.BR mice treated with formolized BF. The stimulation of immunoglobulin production after BF treatment was accompanied by changes in the levels of enterocyte brush-border enzymes; this responsiveness to BF treatment was genetically regulated.

• MeSH
• Alkaline Phosphatase metabolism   MeSH
• Bacillus immunology   MeSH
• beta-Galactosidase metabolism   MeSH
• Dipeptidyl Peptidase 4 metabolism   MeSH
• Enterocytes enzymology   microbiology   MeSH
• Genetic Predisposition to Disease MeSH
• Glucan 1,4-alpha-Glucosidase metabolism   MeSH
• Germ-Free Life MeSH
• Immunoglobulin A biosynthesis   blood   MeSH
• Immunohistochemistry MeSH
• Lactase MeSH
• Microvilli enzymology   MeSH
• Mice, Inbred BALB C MeSH
• Mice MeSH
• Sucrase metabolism   MeSH
• Intestines enzymology   immunology   microbiology   MeSH
• Intestinal Mucosa enzymology   immunology   microbiology   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Alkaline Phosphatase MeSH
• beta-Galactosidase MeSH
• Dipeptidyl Peptidase 4 MeSH
• Glucan 1,4-alpha-Glucosidase MeSH
• Immunoglobulin A MeSH
• Lactase MeSH
• Sucrase MeSH

3-day-old miniature piglets were stimulated in vivo with Bacillus firmus by the intraperitoneal or intragastric route for 1 d. Cells containing IgA and IgG2 were detected in the ileum in all stimulated but not in control animals. The frequency of blood CD3+ cells increased after intraperitoneal administration of B. firmus, the ratio of polymorphonuclears to lymphocytes increased in all stimulated piglets. B. firmus induced antitumor immunity in rats with transplanted Yoshida sarcoma cells. Granular lymphocytes and dead tumor cells were found in peritoneal exudate of stimulated animals. B. firmus induced IFN-gamma synthesis in human blood lymphocytes stimulated in vitro for 1 d. The amount of TNF-alpha produced by these stimulated human peripheral blood mononuclears (PBMC) was lower than that of PBMC stimulated with some other bacterial immunomodulators. Cells containing TGF-beta or IL-8 were not found in human PBMC stimulated with B. firmus.

• MeSH
• Adjuvants, Immunologic pharmacology   therapeutic use   MeSH
• Bacillus immunology   MeSH
• Bacterial Vaccines pharmacology   therapeutic use   MeSH
• Intubation, Gastrointestinal MeSH
• Ileum immunology   MeSH
• Immunoglobulin A biosynthesis   MeSH
• Immunoglobulin G biosynthesis   MeSH
• Immunotherapy * MeSH
• Injections, Intraperitoneal MeSH
• Interferon-gamma biosynthesis   MeSH
• Rats MeSH
• Cells, Cultured MeSH
• Leukocytes, Mononuclear drug effects   metabolism   MeSH
• Humans MeSH
• Swine, Miniature MeSH
• Rats, Wistar MeSH
• Swine MeSH
• Sarcoma, Yoshida therapy   MeSH
• Tumor Necrosis Factor-alpha biosynthesis   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Adjuvants, Immunologic MeSH
• Bacterial Vaccines MeSH
• Immunoglobulin A MeSH
• Immunoglobulin G MeSH
• Interferon-gamma MeSH
• Tumor Necrosis Factor-alpha MeSH