No abstract

Microbiota and its induced inflammation in colorectal mucosa have been considered risk factors for the development of colorectal carcinogenesis. Previous studies demonstrated that the coexisting elements of microbiota in the gut, such as short chain fatty acids (SCFAs) and lipopolysaccharides (LPS), which exhibited regulatory effects on the intestinal epithelial cells individually. Unfortunately, the association between butyrate and the toll-like receptor (TLR) signaling pathway in the development of colon cancer is not fully elucidated. In the present study, by culturing human colon cancer SW480 cells or mouse colon cancer CT26 cells with butyrate and/or TLR4 ligand LPS in vitro, it was identified that butyrate suppressed the growth and promoted apoptosis of these cancer cells. Notably, the expression levels of TLR4 and CD14 were markedly increased on these butyrate-treated cells, but not on LPS-alone treated cells. Additionally, butyrate treatment induced the phosphorylation of extracellular signal-regulated kinase, tumor protein 38, c-Jun NH2-terminal kinase and nuclear factor-κB (NF-κB) p65, and then promoted the pro-inflammatory cytokine tumor necrosis factor-α, but not interleukin 6 secretion in SW480 and CT26 cells. Therefore, butyrate treatment regulates the expression of TLR4, mitogen-activated protein kinase and NF-κB signal pathway activation and pro-inflammatory response in vitro. Although the exact mechanisms have not been fully explored, these results suggested that butyrate and LPS-TLR4 signaling mediated innate immunity in colon cancer cells through two distinct but inter-regulated pathways. Thus, butyrate can further initiate innate immunity against tumor cells by upregulating the TLR4 expression and activation to preserve intestinal homeostasis.

SummaryAccumulating data show that the phenotypes and functions of distinctive mucosal dendritic cells (DCs) in the gut are regulated by retinoic acid (RA). Unfortunately, the exact role of butyrate in RA-mediated mucosal DC differentiation has not been elucidated thoroughly to date. Mucosal-like dendritic cell differentiation was completed in vitro by culturing bone marrow cells with growth factors [granulocyte-macrophage colonystimulating factor (GM-CSF/interleukin (IL)-4], RA and/or butyrate. The phenotypes, cytokine secretion, immune functions and levels of retinal dehydrogenase of different DCs were detected using quantitative polymerase chain reaction (qPCR), enzyme-linked immunosorbent assay (ELISA) and flow cytometry, respectively. The results showed that RA-induced DCs (RADCs) showed mucosal DC properties, including expression of CD103 and gut homing receptor a 4 b 7 , low proinflammatory cytokine secretion and low priming capability to antigen-specific CD4 1 T cells. Butyrate-treated RADCs (Bu-RA-DCs) decreased CD11c, but increased CD103 and a 4 b 7 expression. Moreover, the CD4 1 T priming capability and the levels of retinal dehydrogenase of RA-DCs were suppressed significantly by butyrate. Thus, butyrate and retinoic acid have different but synergistic regulatory functions on mucosal DC differentiation, indicating that immune homeostasis in the gut depends largely upon RA and butyrate to imprint different mucosal DC subsets, both individually and collectively.

Diets rich in n-3 polyunsaturated fatty acid (n-3 PUFA) fish oil (FO) have beneficial effects in obesity‑associated metabolic disease. However, contradictory roles in inflammatory disease intervention have been reported. Our previous work revealed that a high‑FO diet promoted myeloid cell differentiation by modifying the bone marrow microenvironment; however, its effects on liver inflammation and complement system activation remain unknown. By performing ELISA, reverse transcription‑quantitative polymerase chain reaction, flow cytometry and histology on mice fed with high‑FO and low‑fat diets, the present study demonstrated that a 4‑week high‑FO diet promoted liver inflammation in mice without affecting body or liver weight. The livers of high‑FO diet mice exhibited increased infiltration of T cells and CD11b+ Gr‑1+ myeloid cells. Additionally, a higher level of IL‑1β and MCP‑1 mRNA expression was detected, suggesting that the high‑FO diet promoted liver inflammation. Further experiments indicated that the high‑FO diet increased the total hemolytic complement activity (CH50), promoted the production of the membrane attack complex and increased the levels of various complement proteins in vivo, including complement components C3, C4b, C1qb and factor B. Furthermore, higher concentrations of triglyceride were detected in the peripheral blood of high‑FO diet mice, indicating the potential protective roles of n‑3 PUFAs in FO against lipotoxicity in hyperlipidemia. Collectively, the present study demonstrated that high FO intake induced inflammation and activated the complement system in the liver. However, further study is required to determine the exact mechanisms.

Food allergy prevalence has steadily increased worldwide over the past decades and immunotherapeutic treatment strategies are gaining attention. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) exhibit similar immune regulatory properties to bone marrow-derived MSCs. hUC-MCSs can be prepared with fewer ethical constraints and are potential candidates for allergic disorder therapies. The current study aimed to investigate potential antiallergic properties of hUC-MSCs in mice with ovalbumin (OVA)-induced food allergy. Administration of hUC-MSCs cells intraperitoneally combined with oral gavage of the culture medium significantly alleviated OVA-induced diarrhea symptoms. Additionally, this treatment significantly decreased IgE levels and the percentage of T helper 2 cells in the blood, which were increased in mice with OVA-induced food allergy. The mRNA levels of the inflammatory cytokines interleukin-4 and tumor necrosis factor-α, and inflammatory cell infiltration in mouse colons were significantly decreased in hUC-MSCs-treated animals compared with mice with OVA-induced food allergy. Goblet cells were detected in colons of allergy-induced mice and their numbers were reduced following treatment with hUC-MSCs. In addition, treatment with hUC-MSCs reestablished the gut flora. The results revealed that hUC-MSCs may have a potential application in food allergy therapy.