Dietary fiber, with intake of soluble fibers in particular, has been reported to lower the risk for developing inflammatory bowel diseases (IBD). This is at least partly attributable to the fermentation of dietary fiber by the colonic microbiota to produce short chain fatty acids. Pectin, a widely consumed soluble fiber, is known to exert a protective effect in murine models of IBD, but the underlying mechanism remains elusive. Apart from having a prebiotic effect, it has been suggested that pectin direct influences host cells by modulating the inflammatory response in a manner dependent on its neutral sugar side chains. Here we examined the effect of the side chain content of pectin on the pathogenesis of experimental colitis in mice. Male C57BL/6 mice were fed a pectin-free diet, or a diet supplemented with characteristically high (5% orange pectin) or low (5% citrus pectin) side chain content for 10-14 days, and then administered 2,4,6-trinitrobenzene sulfonic acid or dextran sulfate sodium to induce colitis. We found that the clinical symptoms and tissue damage in the colon were ameliorated in mice that were pre-fed with orange pectin, but not in those pre-fed with citrus pectin. Although the population of CD4 + Foxp + regulatory T cells and CD4 + RORγt + inflammatory T cells in the colon were comparable between citrus and orange pectin-fed mice, colonic interleukin (IL)-1β and IL-6 levels in orange pectin-fed mice were significantly decreased. The fecal concentration of propionic acid in orange pectin-fed mice was slightly but significantly higher than that in control and citrus pectin-fed mice but the cecal concentration of propionic acid after the induction of TNBS colitis was comparable between orange and citrus pectin-fed mice. Furthermore, the protective effect of orange pectin against colitis was observed even in mice treated with antibiotics. IL-6 production from RAW264.7 cells stimulated with the toll-like receptor agonist Pam3CSK4 or lipopolysaccharide was suppressed by pre-treatment with orange pectin in vitro. Taken together, these results suggest that the side chains of pectin not only augment prebiotic effects but also directly regulate IL-6 production from intestinal host cells in a microbiota-independent fashion to attenuate colitis.

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Binding of class I MHC molecules (MHCI) to an inhibitory receptor, PIR-B, expressed on B cells and myeloid cells provides; also known as class I H-2 and HLA in mice and humans, respectively) (6). Because MHCI are expressed ubiquitously, the binding to MHCI causes PIR-B to deliver a constitutive inhibitory signal via recruitment of tyrosine phosphatase, Src homology 2 domain-containing tyrosine phosphatase-1 (7-9), whose substrates are critical cytosolic signaling molecules such as Bruton's tyrosine kinase (10). Similar to other stimulatory and inhibitory receptor pairs with shared ligand-binding specificities (11), PIR-B expression usually takes place concomitantly with that of the activating-type isoform PIR-A although the physiological role of PIR-A in the immune system remains largely unknown.Recent unexpected findings have revealed additional inhibitory roles of PIR-B in synaptic plasticity (12) and axonal regeneration (13) in the neuronal system. In mice lacking functional PIR-B, the cortical ocular dominance plasticity is more robust, indicating that PIR-B functions to limit the extent of experience-dependent plasticity in the visual cortex and suggesting that it may function broadly to stabilize neuronal circuits (12). Surprisingly, it has also been reported (13) that PIR-B can bind to three axonal outgrowth inhibitory proteins in oligodendrocytes, i.e. neurite outgrowth inhibitor protein (Nogo) (14), myelin-associated glycoprotein (MAG) (15, 16), and oligodendrocyte myelin glycoprotein (OMgp) (17), like the Nogo receptor does (18,19). Interfering with PIR-B activity, either with antibodies or by genetic deletion of the cytoplasmic portion of PIR-B, partially reverses the neurite inhibition by Nogo, MAG, and OMgp, implying that PIR-B mediates the regeneration blocking of axons (13).Given the two kinds of physiological ligands for PIR-B, i.e. MHCI and neurite outgrowth inhibitor proteins, we were

We studied the effects on 25 analytes of duration of contact of serum with non-anticoagulated blood and of temperature. Serum was separated after blood was allowed to stand, for 0, 2, 4, 6, 8, 24, or 48 h at 4, 23, or 30 degrees C. Results obtained for bilirubin, albumin, zinc sulfate turbidity, thymol turbidity, cholinesterase (EC 3.1.1.8), alkaline phosphatase (EC 3.1.3.1), leucine aminopeptidase (EC 3.4.11.1), amylase (EC 3.2.1.2), total cholesterol, triglycerides, beta-lipoprotein, serum urea nitrogen, creatinine, uric acid, and gamma-glutamyltransferase (EC 2.3.2.2) were not influenced by storage at 4, 24, or 30 degrees C for as long as 48 h. Negligible differences were seen for potassium in sera in contact with cells as long as 24 h at 23 degrees C and for inorganic phosphorus after 48 h at 4 degrees C. However, at 4 degrees C we noted an increase at 8 h, a slight decrease at 30 degrees C. Statistically significant changes were seen for total protein and calcium after 48 h at 30 degrees C; for aspartate aminotransferase (EC 2.6.1.1), and alanine aminotransferase (EC 2.6.1.2), between 8 and 24 h at 23 degrees C and as soon as 6 h at 30 degrees C; for lactate dehydrogenase (EC 1.1.1.27) after 8 h at 30 degrees C and between 8 and 24 h at 23 degrees C; for glucose at 24, 4, or 2 h of storage at 4, 23, or 30 degrees C, respectively; for inorganic phosphorus after 48 h at 23 degrees C or 8 h at 30 degrees C; for potassium after 4 h at 4 degrees C or 24 h at 30 degrees C; and for sodium after 48 h at 4 degrees C or 6 h at 23 or 30 degrees C.

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