The experiment demonstrated that hASCs are one of the important regulators of immune tolerance with the capacity to suppress effector T cells and to induce the generation of antigen-specific Treg cells. Autoimmune inner ear disease (AIED)1,2 is described as progressive, bilateral although asymmetric, sensorineural hearing loss that can be improved by immunosuppressive therapy. It is widely recognized that autoimmune mechanisms are involved in inner ear diseases.2 Tuohy and colleagues3 demonstrated that patients

with AIED have higher frequencies of interferon-γ (IFN-γ)-producing T cells and higher serum antibody titres compared with both control subjects with normal hearing and patients with noise- and/or age-related

hearing loss. Many autoantigens have been implicated as possible causal antigens in AIED: heat-shock protein 70,4,5 collagen II,6,7 cochlin3,8 and, most recently, β-tubulin.9–13 Carfilzomib clinical trial Yoo et al. demonstrated Pembrolizumab that 67 (59%) out of 113 patients with Ménière’s disease had antibodies to a 55 000 molecular weight protein β-tubulin in guinea-pig inner ear extract.9–13 Moreover, immunohistological studies showed that β-tubulin appears to be the highly expressed protein in inner ear tissues, such as hair cells, supporting cells, spiral ligament of stria vascularis, the neural pathway of the cochlea, as well as the spiral ganglion, indicating that β-tubulin is a fundamental protein in guinea-pig inner ear.9,12 Nevertheless,

inner ear immunization with β-tubulin changed its spatial distribution in specific structures12 and caused degeneration of the spiral ganglion,12 thereby Org 27569 affecting the functions of microtubules in the stria vascularis and the spiral ganglion. More recently, Cai et al.13 developed a form of experimental autoimmune hearing loss (EAHL) by immunizing BALB/c mice with recombinant mouse β-tubulin. Mice immunized with β-tubulin developed substantial hearing loss and loss of hair cells in the basal turn of the cochlea. However, peripheral tolerance could be induced by oral administration of low-dose β-tubulin antigen in an animal model of AIED.13 This treatment showed less hearing loss and less inner ear damage; decreased IFN-γ secretion in response to β-tubulin antigen; and demonstrated an effective, antigen-specific method to suppress EAHL. Mesenchymal stem cells (MSCs) are mesoderm-derived cells that reside in virtually all tissues and function as precursors of non-haematopoietic connective tissues with the capacity to differentiate into mesenchymal and non-mesenchymal cell lineages.14–16 Besides their potential clinical application to repair damaged tissues, bone marrow-derived MSCs (BM-MSCs) have recently been described as potent immunomodulators in various immune disorders, including inhibition of dendritic cell maturation, T-cell proliferation and B-cell function.

Hence, further studies are needed to characterize the influence of hormones on nTreg. Taken together, we could demonstrate that nTreg isolated from peripheral blood distinctly suppress Th1 cells, but not Th2 or Th17 cells. We also showed that nTreg secrete IL-10 and IL-17A but almost no IL-2, IL-4,

IFN-γ or TNF-α. Additionally, nTreg produced IL-6, which is known as a critical factor in breaking nTreg-mediated tolerance and in the development LBH589 clinical trial of nTreg and Th17 cells.17,18,41 Furthermore, we discovered the presence of a diurnal cycle dynamic that affects the abilities of Tres to generate cytokines and nTreg to suppress cytokine secretion. Additionally, our data indicate that the diurnal rhythm of cytokine secretion by Tres might be partially regulated by cortisol and prolactin. In conclusion, our data demonstrate that not only does the migration of leucocytes in the peripheral blood change over a diurnal cycle but also the function of defined T-cell subsets. This finding is novel and it will be interesting to study the effect of the diurnal rhythm of T-cell function on diurnal immune responses in relation to autoimmunity, allergy and vaccination. We declare that none of the authors has any financial conflict of interest. We are grateful to Susanne Diekelmann, Stojan Dimitrov, and Ines Wilhelm, Dept. of Neuroendocrinology, University of Luebeck for helping INCB024360 clinical trial us with the planning of the study design

and the sleep lab protocol and Monika Bajtus for lab work. We thank Dr. Andreas Katopodis at the Novartis Institutes of Biomedical Research for providing basiliximab (Simulect®). We also thank Jochen Hühn (Helmholtz Center, Braunschweig, Germany), Nina Oberle (Deutsches Krebsforschungszentrum, Heidelberg) and Antje Müller (Rheumatology, University of Luebeck) for helpful scientific discussions. We also thank Bernhard Gibbs (Medway School of Pharmacy, University of Kent) for editing our manuscript. This work was funded by the DFG, SFB 654, project

C6 and C8, SFB/TR 22, and the E37-2008 grant of the University of Luebeck. next Figure S1. Suppression of cytokine secretion of CD4+ CD25- responder T cells by CD4+ CD25high natural regulatory T cells. CD4+ CD25- responder T cells (Tres, mean purity (MACS® + Sort): 99.2 ± 0.5%) and CD4+ CD25high natural regulatory T cells (nTreg, mean purity (MACS® + Sort): 98.5 ± 0.6%) were isolated from peripheral blood of healthy young men which was sampled at 8:30 hr. Cultures of Tres with or without nTreg or cultures of only nTreg were stimulated with αCD3-mAb, supernatants were collected after 62 hr and the cytokine concentration of IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL10, and IL-17A was analyzed. Data represent mean values ± standard error of the mean (n = 6). P < 0.05* Figure S2. Proliferation of CFSE stained CD4+ CD25high natural regulatory T cells in co-culture with CD4+ CD25- responder T cells. CD4+ CD25- responder T cells (Tres, purity (MACS® + Sort): 99.

Results:  Our approach yields human pericytes that may be serially expanded in culture and that uniformly express the cellular markers NG2, CD90, CD146, α-SMA, and PDGFR-β, but lack markers of smooth muscle cells, endothelial cells, and leukocytes. When co-implanted with human endothelial cells into C.B-17 SCID/bg mice, human pericytes invest and stabilize developing human endothelial cell-lined microvessels. Conclusions:  We conclude that our method for culturing pericytes from human placenta results in the expansion of functional pericytes that may be used to study a variety of questions related to vascular biology. “
“Please cite this paper as: Olfert and Birot (2011).

Importance of PI3K Inhibitor Library manufacturer Anti-angiogenic Factors in the Regulation of Skeletal Muscle Angiogenesis. Microcirculation 18(4), 316–330. The microcirculation is essential for delivery of oxygen and nutrients to maintain skeletal muscle health and function. The network of microvessels surrounding skeletal myocytes has a remarkable plasticity that ensures a good match between muscle perfusion capacities and myofiber metabolic needs. Depending on physiologic conditions, this vascular plasticity can either involve

growth (e.g., exercise-induced angiogenesis) or regression (e.g., physical deconditioning) of capillaries. This angio-adaptative response is thought to be controlled by a balance between pro- and anti-angiogenic factors and their receptors. While changes in the expression or activity for pro-angiogenic Hydroxychloroquine molecular weight factors have been well studied in response to acute and chronic exercise during the past two decades, little attention thus far has been devoted to endogenous negative regulators that are also likely to be important in regulating capillary growth/regression. Indeed, the importance and contribution of anti-angiogenic

factors in controlling skeletal muscle angiogenesis remains poorly understood. Here, we highlight the emerging research related to skeletal muscle expression of several negative angiogenic factors and discuss their potential importance in controlling skeletal muscle angio-adaptation, particularly in physiologic response click here to physical activity. “
“Please cite this paper as Hill CE. Long distance conduction of vasodilation: a passive or regenerative process? Microcirculation 19: 379-390, 2012. The mechanism enabling coordination of the resistance of feed arteries with microcirculatory arterioles to rapidly regulate tissue blood flow in line with changes in metabolic demand has preoccupied scientists for a quarter of a century. As experiments uncovered the underlying electrical events, it was frequently questioned how vasodilation could conduct over long distances without appreciable attenuation.

Thus, while ASC gain immunosuppressive capacity under inflammatory conditions, their regenerative capacity is preserved. A suggested undesired property of ASC is their potential transformation into fibrosis [36]. We found that culture of ASC with MLR had no effect on collagen gene expression, while culture of ASC with proinflammatory cytokines induced down-regulation

of the expression of multiple collagens. The expression of connective tissue growth factor, TGF-β and platelet-derived growth factor, which can induce epithelial–mesenchymal transition, was not affected by inflammatory conditions. This suggests that inflammatory conditions do not favour the induction of fibrosis by ASC. buy Olaparib The present study demonstrates that the type of inflammatory stimulus affects the response of ASC. In an alloactivated setting, ASC remain functional and even enhance their immunosuppressive function. Their immunosuppressive activity can be enhanced further by culturing ASC with proinflammatory cytokines. This offers the possibility to generate ASC in vitro with strong and instant

immunosuppressive capacity. The potential regenerative capacity of U0126 solubility dmso ASC is not affected by inflammatory conditions and there is no evidence for an increased risk of fibrosis. Therefore, immune activation of ASC could be of benefit for potential clinical immune therapy with ASC. The authors thank the Department of Surgery of the Erasmus Medical Center Rotterdam for collecting the perirenal adipose tissue of the living kidney donors. We also thank Zeliha Ozgur for technical assistance. Microarray data are deposited in Gene Expression Omnibus (GEO), number GSE18662 at http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE18662 (free, accessible from 20 October 2010). The authors have nothing to disclose. “
“Thymic epithelial cells

(TECs) provide key instructive signals for T-cell differentiation. Thymic cortical (cTECs) and medullary (mTECs) epithelial cells constitute two functionally distinct microenvironments for T-cell development, which derive from a common bipotent TEC progenitor. While seminal studies have partially elucidated events downstream of bipotent TECs in relation to the emergence Phosphoprotein phosphatase of mTECs and their progenitors, the control and timing of the emergence of the cTEC lineage, particularly in relation to that of mTEC progenitors, has remained elusive. In this review, we describe distinct models that explain cTEC/mTEC lineage divergence from common bipotent progenitors. In particular, we summarize recent studies in mice providing evidence that mTECs, including the auto-immune regulator+ subset, derive from progenitors initially endowed with phenotypic properties typically associated with the cTEC lineage.

falciparum, as revealed by genome-wide analyses of parasite expression profiles in response to stress (59–61). The concept of transcriptional

CP-690550 concentration rigidity in Plasmodium was recently conceived (59). Parasites subjected to chemical or environmental stresses do not specifically compensate for the stress-targeted pathways at the transcriptional level; instead, they exhibit a strong cell cycle arrest and an induction of genes involved in general (nonspecific) stress responses and sexual differentiation. Taken together, these studies highlight an unusual method of transcriptional regulation with a limited capacity for positive or negative feedback mechanisms. Additional analyses of mRNA vs. protein profiles show significant varying time shifts between transcript and protein levels. These data enforce that extensive post-transcriptional mechanisms of gene regulation may have important roles during parasite development (38,62,63). Following these latest observations, the characterization of protein complexes involved in translational repression (64) and whole-genome

analysis of mRNA decay rates strongly supports the idea that post-transcriptional regulation may be an important mechanism for gene regulation in P. falciparum (65). Recent studies selleck inhibitor highlight the importance of key chromatin components that regulate parasite development (53,66,67). A large number of chromatin-modifying complexes have recently been identified [reviewed in (68)] leading to the hypothesis that malaria parasites may, in large part, be subject to epigenetic mechanisms that control gene expression. Epigenetic MYO10 modifications involve reversible modifications to DNA or proteins that do not affect the genome sequence but are inheritable and modulate gene expression as well as other biological processes (69). In the human malaria parasite, heterochromatic

silencing was shown to control mutually exclusive expression of antigenic variation genes in the parasite (66,67,70). More recently, several studies investigated the genome-wide distribution of various euchromatic/heterochromatic histone marks. Lopez-Rubio et al. (71) used high-resolution ChIP-on-chip to map the positions of trimethylated lysine 9 histone H3 (H3K9me3), trimethylated lysine 4 histone H3 (H3K4me3) and acetylated lysine 9 histone H3 (H3K9ac) in P. falciparum. They showed that H3K9me3, a silencing mark, has an atypical distribution in the P. falciparum genome; H3K9me3 is indeed confined within the subtelomeric and limited chromosome internal regions that are closely associated with genes involved in antigenic variation. On the contrary, the active marks, H3K4me3 and H3K9ac, display a broad distribution across the genome.

85–23, revised 1985) and the national laws on Protection of Animals were followed. A total of 109 female NOD mice were analysed. First, 62 female NOD mice were litter-matched and randomized after weaning into four groups (groups A1–D1; Fig. S1). As

a control group, female NOD mice in group A1 (n = 16) were not mated. In the remaining groups, female NOD were mated at age 10 weeks to male NOD mice (group B1, n = 15) representing MHC identical mating, male CByB6F1/J mice (group C1, n = 16) representing MHC haploidentical mating or male C57BL/6J mice (group D1, n = 15), representing fully MHC mismatched mating. For pairings, two male mice were used in each group. To analyse the effect of later gestation, a second set of 47 female NOD mice were litter-matched and randomized after weaning into three groups: control unmated females (n = 16, group A2); females mated at

age 13 weeks to three male Ferrostatin-1 mw NOD mice (n = 16, group B2); and females mated at age 13 weeks to three male CByB6F1/J mice (n = 15, group C2). For the mating, two female and one male mouse were housed together in one cage for a median time of 14 days [interquartile range (IQR), 14–17 days]. Subsequently, 45 of 46 females mated at 10 weeks of age and 29 of 31 females mated at 13 weeks of age delivered altogether 610 pups. The number of pups per litter ranged between four and 13 (median, 9; IQR, 7–10), and the offspring numbers were distributed equally between the different mating groups (Fig. S1). All pups remained with their dam for the weaning period of median 21 days (IQR, 21–23 days). All female Fulvestrant NOD mice were followed to overt diabetes or until the age of 28 weeks. Histone demethylase Urine glucose levels were measured twice weekly using urine glucose sticks (Diastix, Bayer HealthCare LLC, Mishawaka, IN, USA), beginning at 10 weeks of age. The diagnosis of diabetes was defined as two consecutive urine glucose values > 5·5 mmol/l and blood glucose levels > 13·9 mmol/l (Glucometer Elite,

Bayer Diagnostics GmbH, Munich, Germany). Venous blood was obtained at age 10 weeks (prior to the mating) and 16 weeks (after weaning), and diabetes onset or 30 weeks for the measurement of insulin autoantibodies. In group C1, splenocytes from two diabetic mice at diabetes onset and two non-diabetic mice at the end of observation were collected to look for lymphocyte chimerism. Antibodies to insulin were detected using a radiobinding assay, as described previously [14]. All measurements were performed on coded samples that were operator-blinded. The upper limit of normal was determined from the 99th centile values obtained in sera from BALB/c and C57BL/6 female mice. The assay is represented as laboratory B in the animal models of Diabetes Workshop [15]. In order to analyse if cells with paternal genome alleles migrated during gestation from the fetus to the dam and persisted, staining and flow cytometry for MHC class I molecules was performed on the collected splenocytes.

2×106 COS-7 cells seeded in 100-mm plates were transfected with 5 μg p3×FlagBTN3Ax BMN 673 cost constructs using 15 μL of FuGENE 6 Transfection Reagent (Roche). The human NK cell line, KHYG-1 is growing in RPMI 1640 medium supplemented with 20%

FCS and 450 UI/mL rIL-2 25. 5×106 KHYG-1 cells were transfected with 2 μg p3×FlagBTN3Ax constructs using the Amaxa™ Nucleofector™ Technology (Solution T, program Y-001) (Lonza Cologne AG). Public and home-made Affymetrix U133+2 data sets of purified CD4, CD8 and NK cells were collected. CD8 and CD4 data were retrieved from the public GEO data sets 26 (http://www.ncbi.nlm.nih.gov/gds), while NK sets were personal. We used Robust Multichip Average (RMA) with the non-parametric quantile algorithm as normalization parameter. RMA was applied to the raw data collected from the various series. Quantile normalization and Loess’ correction were carried out in R using Bioconductor and associated packages. The probe set corresponding to the three isoforms of BTN3A was retrieved from the normalized data sets and the corresponding log values were linearized for graphical representation. We used the respective Affymetrix Palbociclib ic50 probe sets corresponding

to BTN3A1, BTN3A2 and BTN3A3 isoforms: STP201623_s_at, 213282_at, 204171_at. Human CD4+ T cells were purified by negative selection from PBMCs using magnetic beads (Miltenyi Biotec) according to the manufacturer’s protocol. CD4+ T cells were routinely more than 97% pure. Cells were incubated 24 h in RPMI 1640 10% FBS at 37°C. CD4+ T cells were washed with PBS 1% FCS and stimulated with aAPCs at a ratio of 1:3 (cells to beads) comprised of magnetic beads (Dynabeads M-450 Epoxy, Dynal Biotech) coated with anti-CD3, anti-CD28 and/or anti-CD277 mAbs as described above. The contacts between cells (106 in 50 μL) and beads

(3×106 in 30 μL) are performed at 37°C in water bath for different times (2, 5, 10 and 30 min) in PBS 1% FCS. Phosphoflow analysis was performed by cytometry as previously described 27. Briefly, cells were fixed and permeabilized, incubated with anti-phospho-Akt tuclazepam S473 (#4058, Cell Signaling Technology) or anti-phospho-ERK-1/2 T202/Y204 (#4377, Cell Signaling Technology) antibodies and appropriate biotinylated secondary antibodies. Finally, revelation was performed using Streptavidin–phycoerythrin solution (#IM3325, Beckman Coulter). FACS data were acquired on an FACS Canto flow cytometer (BD Biosciences) using the Diva software. FACS data were analyzed using the Flowjo software (TreeStar, Ashland, OR, USA). All data were analyzed using GraphPad Prism version 5.00 for (GraphPad, San Diego, CA, USA) and Microsoft Excel (Microsoft Office). The Mann–Whitney test-matched non-parametric test was used to examine: the variations of CD277 and PD-1 expression from lymphoid tissue on living T lymphocyte subsets (in Fig. 1, Supporting Information Figs.

Consequently, the finding needs to be confirmed in a larger sample that includes more patients with thymic alteration. Our result confirmed the correlation between the frequency of periphery Th17 cells and the Etoposide nmr concentration of AChR antibodies of patients with MG. However, the AChR concentration has no relationship with the subtype of MG. But the number of Th17 cells with MG patients may be associated with certain thymic pathology changes or pathological subtype. Moreover, we further detected the evolution of Th17 cells (%) in the peripheral blood after thymectomy in 10 MG patients with TM. There was a trend towards decreased population of

Th17 cells (%), although this did not reach statistical significance (data not shown). IL-17A is the hallmark cytokine of Th17 cells and has been shown to Dactolisib mouse function as a proinflammatory cytokine that upregulates a number of chemokines and matrix metalloproteases, leading to the recruitment of neutrophils into sites of inflammation [24]. We found that the expression of IL17 and serum IL-17 levels were markedly higher in patients with TM than those of the HC. But there were no significant differences between HC and TH or NT. Thus, the observed increase in Th17 cells in our patients with MG may represent a thymoma-specific phenomenon.

Taken together, these results indicate that Th17 cells are closely associated with the immune injury induced by TM. Development of Th17 phenotypes requires the presence of TGF-β in addition to the presence of IL-6. However, we failed to find significant difference in the level of TGF-β and IL-6 between patients with MG and HC. It has been demonstrated that IL-23 bridging the IL-17 cytokine family leads to the identification of the Th17 lineage [25]. Others also recently characterized that IL-23 is considered currently to play a role in maintaining Th17 cell survival [19,

26]. Kobayashi [27] found that IL-17 production was significantly increased by IL-23 in lamina propria CD4+ cells from ulcerative colitis (UC), and upregulated IL-23p19 mRNA expression was correlated with IL-17 in UC. In humans, IL-1β has been implicated as an essential Etomidate cytokine for the Th17 differentiation, as IL-1β in naïve CD4 cells induced retinoic acid–related orphan nuclear hormone receptor c (RORc) expression and Th17 differentiation, which was enhanced by IL-6 and IL-23 [28, 29]. Sutton [30] demonstrated that IL-17A could be induced from γδT cells directly by IL-1 and IL-23 derived from activated DCs. A more recent study indicated that prostaglandin E2 (PGE2) and IL-23 plus IL-1β induce the Th17 immune response preferentially in CD161+ CD4+ memory T cells in inflammatory bowel disease (IBD) [31]. We also found that the expression of two Th17 relative cytokines, IL-1β and IL-23, was upregulated statistically in TM group.

Recent studies have focused on potential abnormalities of the IgA1 molecule as a factor in the pathogenesis of IgAN. Our GWAS identified a INK 128 concentration locus on chromosome 22q12.2 that is associated with elevated levels of serum IgA in patients with IgAN. This locus contains genes encoding leukemia inhibitory factor (LIF) and oncostatin M (OSM), IL-6-related cytokines using gp130 for signal transduction and implicated in mucosal immunity and inflammation. Recently, we found that IL-6/gp130/STAT3 signaling plays an important role in the enhanced production of Gd-IgA1 in IgAN. In this

study, we characterized signaling mechanisms involved in Gd-IgA1 production induced by LIF and OSM, using immortalized IgA1-secreting cells derived from the circulation and tonsils of IgAN patients and healthy controls (HC). Methods: IgA1-secreting cells were stimulated with LIF and OSM and production of IgA1 and Gd-IgA1 was assessed. The role of signaling pathways induced by these cytokines in Gd-IgA1 production was confirmed by using siRNA knock-down and specific inhibitors. Results: Our data demonstrate that LIF and OSM decreased production of IgA1 in both IgAN and HC cells. In contrast, these Akt inhibitor cytokines increased production of Gd-IgA1, but only in cells from IgAN patients. We established that the cytokine signaling was mediated through specific protein

kinase signaling pathways. We confirmed these results by using specific inhibitors of signaling. Some of the tested inhibitors 4��8C reduced production of Gd-IgA1 in IgAN cells in a dose-dependent fashion. siRNA knock-down confirmed the central role of LIF/gp130 signaling pathway in the enhanced production of Gd-IgA1. Conclusion: IgA1-secreting cells from IgAN patients responded abnormally to LIF and OSM, cytokines encoded in a locus identified by GWAS. These results contribute towards understanding the mechanisms involved in production of Gd-IgA1 in IgAN

and can be useful in development of future disease-specific therapy. MORIYAMA TAKAHITO, OSHIMA YASUKO, TANAKA KAYU, IWASAKI CHIHIRO, OCHI AYAMI, KATAOKA HIROSHI, ITABASHI MITSUYO, TAKEI TAKASHI, UCHIDA KEIKO, NITTA KOSAKU Tokyo Women’s MEdical University Introduction: Little is known about the long-term prognosis of patients with IgA nephropathy (IgAN). Methods: This retrospective cohort analysis evaluated clinical and histological findings at the time of renal biopsy, initial treatment, patient outcomes over 30 years, and risk factors associated with progression in 1,012 IgAN patients diagnosed at our center since 1974. Results: Of the 1,012 patients, 40.5% were male. Mean patient age was 33 ± 12 years and mean blood pressure was 122 ± 17/75 ± 13 mmHg. Mean serum creatinine concentration was 0.89 ± 0.

Correlation between CgA and TNF receptor-I (TNFR-I) and TNFR-II has been evaluated in patients before the initiation of treatment with Infliximab® and compared it with the value calculated Selleck SCH772984 during treatment [74]. The authors observed a high correlation between

CgA and both receptors. Moreover, they found that treatment with anti-TNF-α monoclonal antibodies (mAbs) abrogated the correlation between CgA and TNFR-I and TNFR-II, but it should be mentioned that in this study anti-TNF-α mAbs treatment did not modify the mean levels of CgA and TNFRs but led only to the abrogation of the correlation between CgA and TNFRs, implying that perhaps other indirect factors are associated in this effect. Three years later, the same group described that patients with RA have significantly higher serum levels of CgA

and TNFRs compared with controls and that the highest levels of CgA identify the population of patients with extra-articular manifestations [74]. Taken together, these results suggest that CgA might be involved in the pathogenesis of inflammatory autoimmune disease through a complex interaction with TNF-α, mediated by as yet-undefined factors. In a series of papers Metz-Boutigue’s group, who have published extensively on granins, showed a link between serum concentration of CgA and outcome in patients admitted with or without systemic Tyrosine Kinase Inhibitor Library cell assay inflammatory response syndrome. CgA concentrations were correlated positively with inflammation markers such as procalcitonin and C-reactive protein, but also with simplified acute physiological score (SAPS). A Cox Glycogen branching enzyme model confirmed that CgA and SAPS were independent predictors of outcome [75,76]. In addition, a significant association has been reported between CgA level and periodontitis, again

showing a close relationship between the level of CgA and the inflammatory process [77]. The hypothesis that Cgs-derived peptides are involved in mechanisms modulating altered colonic motility and visceral pain induced by gut inflammation was tested for the first time in 2004 using an application of acetic acid (AA) in vitro and in vivo. Using the writhing test, a model of somato-visceral pain, we have demonstrated that depending upon the Cgs-derived peptides used (bCgA 4–16, 47–66), they could display pro- and anti-nocicpetive effects [78,79]. In the context of smooth muscle contraction, Cgs-derived peptides modulate the effect of AA on human and rat smooth muscle contraction via a direct action on the calcium L-type channel or towards an indirect action through the enteric nervous system (motorneurone and type-C sensitive fibre) [80,81]. All these data provide proof of concept that Cgs and Cgs-derived peptides seem to play an important role in the development of inflammatory pathologies, and different groups have now focused their attention upon characterizing a mechanistic explanation. The studies discussed in this review provide evidence in favour of a key role of gut hormones in intestinal inflammation.