Water stable nanocoatings of poly(N-isopropylacrylamide)-based block copolymers on culture insert membranes for temperature-controlled cell adhesion.

This study demonstrated the spin-coating of functional diblock copolymers to develop smart culture inserts for thermoresponsive cell adhesion/detachment control. One part of the block components, the poly(n-butyl methacrylate) block, strongly supported the water stable surface-immobilization of the thermoresponsive poly(N-isopropylacrylamide) (PNIPAAm) block, regardless of temperature. The chain length of the PNIPAAm blocks was varied to regulate thermal surface functions.

Confounding effects of microbiome on the susceptibility of TNFSF15 to Crohn's disease in the Ryukyu Islands.

Crohn's disease (CD) involves chronic inflammation in the gastrointestinal tract due to dysregulation of the host immune response to the gut microbiome. Even though the host-microbiome interactions are likely contributors to the development of CD, a few studies have detected genetic variants that change bacterial compositions and increase CD risk. We focus on one of the well-replicated susceptible genes, tumor necrosis factor superfamily member 15 (TNFSF15), and apply statistical analyses for personal profiles of genotypes and salivary microbiota collected from CD cases and controls in the Ryukyu Islands, southernmost islands of the Japanese archipelago.

Fucoidan enhances intestinal barrier function by upregulating the expression of claudin-1.

Aim: To evaluate the protective effects of fucoidan on oxidative stress-induced barrier disruption in human intestinal epithelial cells.

Methods: In Caco-2 cell monolayer models, the disruption of barrier function by oxidative stress is mediated by H₂O₂. The integrity of polarized Caco-2 cell monolayers was determined by measuring the transepithelial resistance (TER) and permeability was estimated by measuring the paracellular transport of FITC-labeled 4-kDa dextran (FD4).

Dysbiosis of salivary microbiota in inflammatory bowel disease and its association with oral immunological biomarkers.

Analysis of microbiota in various biological and environmental samples under a variety of conditions has recently become more practical due to remarkable advances in next-generation sequencing. Changes leading to specific biological states including some of the more complex diseases can now be characterized with relative ease. It is known that gut microbiota is involved in the pathogenesis of inflammatory bowel disease (IBD), mainly Crohn's disease and ulcerative colitis, exhibiting symptoms in the gastrointestinal tract.

Imbalance of NKp44(+)NKp46(-) and NKp44(-)NKp46(+) natural killer cells in the intestinal mucosa of patients with Crohn's disease.

Background & Aims: Mucosal natural killer (NK) cells that produce interleukin (IL)-22 mediate intestinal homeostasis and inflammation in mice. However, their role in the pathogenesis of human inflammatory bowel diseases (IBDs) is not known. We investigated intestinal NK cells in intestinal mucosa samples of patients with Crohn's disease (CD).

Monocyte chemoattractant protein-1 contributes to gut homeostasis and intestinal inflammation by composition of IL-10-producing regulatory macrophage subset.

Lamina propria macrophages (LPMs) spontaneously produce large amounts of anti-inflammatory IL-10 and play a central role in regulation of immune responses against commensal bacteria. MCP-1 is a chemokine that plays an important role in recruitment of monocytes and macrophages to inflamed tissues. We demonstrated that, in addition to IL-10, LPMs produced large amounts of MCP-1, even in a steady state.

TL1A produced by lamina propria macrophages induces Th1 and Th17 immune responses in cooperation with IL-23 in patients with Crohn's disease.

Background: Tumor necrosis factor (TNF)-like protein 1A (TL1A) is a member of the TNF superfamily and contributes to the pathogenesis of Crohn's disease (CD) by stimulating T-helper (Th) 1 cells. In addition to Th1, recent studies have focused on the role of Th17 cells in the pathogenesis of CD. Here we tried to clarify the role of TL1A in Th1 and Th17 immunity in CD.

Human CD14+ macrophages in intestinal lamina propria exhibit potent antigen-presenting ability.

Intestinal APCs are considered critical in maintaining the balance between the response against harmful pathogens and the induction of tolerance to commensal bacteria and food Ags. Recently, several studies indicated the presence of gut-specific APC subsets, which possess both macrophage and dendritic cell (DC) markers. These unique APC subsets play important roles in gut immunity, especially for immune regulation against commensal bacteria.

Dietary histidine ameliorates murine colitis by inhibition of proinflammatory cytokine production from macrophages.

Background & Aims: Elemental diet (ED) is effective for human Crohn's disease (CD). Although some of this effectiveness may be due to its low antigenic load and low fat content, the mechanisms remain unclear. We sought to assess the role of histidine, one of the constituent amino acids of ED, in controlling colitis.

Tetomilast suppressed production of proinflammatory cytokines from human monocytes and ameliorated chronic colitis in IL-10-deficient mice.

Background: Tetomilast (OPC-6535) was originally developed as a compound inhibiting superoxide production in neutrophils. Although its mechanism of action is not completely understood, phosphodiesterase type 4 inhibitory function has been postulated. The therapeutic effect of PDE4 inhibitors has been reported for chronic inflammatory disorders such as chronic obstructive pulmonary diseases.

Unique CD14 intestinal macrophages contribute to the pathogenesis of Crohn disease via IL-23/IFN-gamma axis.

Intestinal macrophages play a central role in regulation of immune responses against commensal bacteria. In general, intestinal macrophages lack the expression of innate-immune receptor CD14 and do not produce proinflammatory cytokines against commensal bacteria. In this study, we identified what we believe to be a unique macrophage subset in human intestine.

Exacerbating role of gammadelta T cells in chronic colitis of T-cell receptor alpha mutant mice.

Background & Aims: T-cell receptor (TCR) gammadelta T cells are an important component of the mucosal immune system and regulate intestinal epithelial homeostasis. Interestingly, there is a significant increase in gammadelta T cells in the inflamed mucosa of patients with ulcerative colitis (UC). However, the role of gammadelta T cells in chronic colitis has not been fully identified.

Lamina propria c-kit+ immune precursors reside in human adult intestine and differentiate into natural killer cells.

Background And Aims: Recent studies have revealed that murine intestinal mucosa contains several kinds of lineage markers (lin)(-) c-kit(+) immune precursor cells. However, immune precursors in the human adult intestine have not been studied extensively.

Methods: Lamina propria mononuclear cells and intraepithelial lymphocytes from surgically resected human adult intestine were examined for the surface antigen expression and cytokine profile by immunohistochemistry and flow cytometry.

Exclusive increase of CX3CR1+CD28-CD4+ T cells in inflammatory bowel disease and their recruitment as intraepithelial lymphocytes.

Background: CX3CL1/Fractalkine (FKN) has been reported to play important roles in various inflammatory diseases. We examined the role of FKN and its receptor CX3CR1 in T-cell migration in the inflammatory bowel diseases (IBDs), ulcerative colitis (UC) and Crohn's disease (CD).

Methods: CX3CR1 expression on peripheral CD4(+) cells from normal controls (NL n = 24) and IBD patients (UC n = 28, CD n = 26) was examined using flow cytometry.

Inhibition of neutrophil elastase prevents the development of murine dextran sulfate sodium-induced colitis.

Background: Neutrophil elastase (NE) is a major secretory product from activated neutrophils and a major contributor to tissue destruction. However, little is known about the pathogenic contribution of NE to ulcerative colitis (UC). This study was designed to investigate the contribution of NE by measuring NE activity in plasma and colonic mucosal tissue from UC patients and a murine acute colitis model, and to elucidate the therapeutic effect of the NE-specific inhibitor ONO-5046.

Nonpathogenic Escherichia coli strain Nissle1917 prevents murine acute and chronic colitis.

Background: Nonpathogenic Escherichia coli strain Nissle1917 has been used as a probiotics in human inflammatory bowel disease; however, there are few reports examining its therapeutic effect on animal colitis models, and its therapeutic mechanisms remain unknown. The aim of this study was to elucidate the therapeutic effect and mechanism of Nissle1917 using murine acute and chronic colitis models.

Methods: Two models were used.