interleukin-8 and Celiac-Disease

Celiac disease (CeD), caused by immune reactions to cereal gluten, is treated with gluten -elimination diets. Within hours of gluten exposure, either perorally or extraorally by intradermal injection, treated patients experience gastrointestinal symptoms. To test whether gluten exposure leads to systemic cytokine production time -related to symptoms, series of multiplex cytokine measurements were obtained in CeD patients after gluten challenge. Peptide injection elevated at least 15 plasma cytokines, with IL-2, IL-8, and IL-10 being most prominent (fold-change increase at 4 hours of 272, 11, and 1.2, respectively). IL-2 and IL-8 were the only cytokines elevated at 2 hours, preceding onset of symptoms. After gluten ingestion, IL-2 was the earliest and most prominent cytokine (15-fold change at 4 hours). Supported by studies of patient-derived gluten-specific T cell clones and primary lymphocytes, our observations indicate that gluten-specific CD4

Topics: Adult; Aged; CD4-Positive T-Lymphocytes; Celiac Disease; Cytokines; Double-Blind Method; Female; Genotype; Glutens; HLA Antigens; Humans; Interleukin-10; Interleukin-2; Interleukin-8; Male; Middle Aged; Placebo Effect; Vomiting; Young Adult

OBJECTIVE. The role of adipokines such as resistin, leptin, and adiponectin could be pivotal in the molecular crosstalk between the inflamed intestine and the surrounding mesenteric adipose tissue. Our aims were to a) evaluate their circulating concentrations in patients with active celiac disease (ACD) and compare them to those in patients with diarrhea-predominant irritable bowel syndrome (IBS-d) and healthy subjects; b) establish the impact of genetic variability in resistin; and c) evaluate whether a 1-year gluten-free diet (GFD) modifies circulating concentrations of resistin, leptin, and adiponectin in celiac patients. MATERIAL AND METHODS. The study included 34 ACD patients, 29 IBS-d patients, and 27 healthy controls. Circulating concentrations of resistin, leptin, adiponectin, IL-6, and IL-8 were evaluated at the time of enrollment. Resistin +299 G/A polymorphism was also analysed. In CD patients, biochemical measurements were repeated after a 1-year GFD. RESULTS. Along with higher IL-6 and IL-8 plasma levels, higher resistin and adiponectin concentrations were found in ACD and IBS-d patients compared with controls (p: 0.0351 and p: 0.0020, respectively). Resistin values proved to be predictable from a linear combination of IL-8 and +299 polymorphism. GFD affected resistin (p: 0.0009), but not leptin and adiponectin concentrations. CONCLUSIONS. Our data suggest that these adipokines are involved in modulating inflammatory processes in both CD and IBS-d patients. Alterations in the adipokine profile as well as the higher prevalence of the resistin +299 G/A SNP A allele compared to controls support the hypothesis that, at least in well-defined cases of IBS, a genetic component may also be supposed.

Topics: Adipokines; Adiponectin; Adult; Aged; Aged, 80 and over; Biomarkers; Case-Control Studies; Celiac Disease; Diarrhea; Diet, Gluten-Free; Female; Genetic Markers; Humans; Interleukin-6; Interleukin-8; Irritable Bowel Syndrome; Leptin; Linear Models; Longitudinal Studies; Male; Middle Aged; Polymorphism, Single Nucleotide; Resistin; Treatment Outcome

Topics: Adult; Aged; Celiac Disease; Chemokine CXCL10; Cytokines; Epitopes, T-Lymphocyte; Female; Gliadin; Glutens; HLA-DQ Antigens; Humans; Immunity, Cellular; Interferon-gamma; Interleukin-2; Interleukin-8; Male; Middle Aged; Peptide Fragments; Peptides; T-Lymphocytes; Young Adult

It is not clear why some patients with coeliac disease (CD) present with severe symptoms and small intestinal mucosal damages while others present with milder symptoms and no frank enteropathy. There is no study to assess the associated factors with mild/severe symptoms and enteropathy. The terminologies like latent, silent and potential are difficult to use and are unrepresentative. In the present study we describe coeliac disease's phenotypes based on HLA haplotypes, IL8 production and past infection with Toxoplasma gondii (T. gondii) infection.. In this case-control study, sera originating from 150 healthy subjects and 150 patients diagnosed with CD during the years 2013-14 were analyzed for the presence of antibodies specific T. gondii of the IgG and IgM subclasses. The level of IL8 were measured and HLA-DQ2 and HLA-DQ8 alleles were genotyped. The correlation between these parameters and the damages in intestinal mucosal were assessed using an accepted histopathological classification.. High levels of IgG antibodies against T. gondii were found in the sera of control group compared to the CD group (52.6% vs. 39.4%, P = 0.02). Mean serum levels of IL8 was significantly higher in CD patients compared with control (P ≤ 0.05). By comparing the level of anti- T. gondii IgG and mucosal damage in celiac disease, we found a significant relationship between the severity of mucosal damages and anti- T. gondii IgG level (P = 0.02). No correlation was detected between Toxoplasma gondii infection and types of HLA (P > 0.05). However, patients with severely abnormal histology carried HLA-DQ2 risk alleles (92 patients (61%)) more often than the controls and those with mild histological abnormalities.. CD patients with severe histological changes had more often Toxoplasma gondii infection than those affected with mild histological features. This suggests that CD's phenotypes are correlated to additional factors like infections and to particular HLA DQ2 alleles that may need additional investigations and potentially will require additional treatment.

Topics: Alleles; Case-Control Studies; Celiac Disease; Haplotypes; HLA-DQ Antigens; Humans; Immunoglobulin G; Interleukin-8; Intestinal Mucosa; Toxoplasma; Toxoplasmosis

The short isoform of thymic stromal lymphopoietin (TSLP), a cytokine constitutively expressed by epithelial cells, is crucial in preserving immune tolerance in the gut. TSLP deficiency has been implicated in sustaining intestinal damage in Crohn's disease. We explored mucosal TSLP expression and function in refractory and uncomplicated coeliac disease (CD), a T-cell-mediated enteropathy induced by gluten in genetically susceptible individuals.. TSLP isoforms-long and short-and receptors-TSLPR and interleukin (IL)-7Rα-were assessed by immunofluorescence, immunoblotting and qRT-PCR in the duodenum of untreated, treated, potential and refractory patients with CD. The ability of the serine protease furin or CD biopsy supernatants to cleave TSLP was evaluated by immunoblotting. The production of interferon (IFN)-γ and IL-8 by untreated CD biopsies cultured ex vivo with TSLP isoforms was also assessed.. Mucosal TSLP, but not TSLPR and IL-7Rα, was reduced in untreated CD and refractory CD in comparison to treated CD, potential CD and controls. Transcripts of both TSLP isoforms were decreased in active CD mucosa. Furin, which was overexpressed in active CD biopsies, was able to cleave TSLP in vitro. Accordingly, refractory and untreated CD supernatants showed higher TSLP-degrading capacity in comparison to treated CD and control supernatants. In our ex vivo model, both TSLP isoforms significantly downregulated IFN-γ and IL-8 production by untreated CD biopsies.. Reduced mucosal TSLP expression may contribute to intestinal damage in refractory and untreated CD. Further studies are needed to verify whether restoring TSLP might be therapeutically useful especially in refractory patients with CD.

Topics: Adult; Aged; Biopsy; Celiac Disease; Cytokines; Duodenum; Female; Fluorescent Antibody Technique; Furin; Humans; Immune Tolerance; Interleukin-8; Intestinal Mucosa; Male; Middle Aged; Protein Isoforms; Receptors, Interleukin-7; Statistics as Topic; T-Lymphocytes; Thymic Stromal Lymphopoietin

Celiac disease (CD) affects approximately 1% of the general population while an estimated additional 6% suffers from a recently characterized, rapidly emerging, similar disease, referred to as non-celiac gluten sensitivity (NCGS). The only effective treatment of CD and NCGS requires removal of gluten sources from the diet. Since required adherence to a gluten-free diet (GFD) is difficult to accomplish, efforts to develop alternative treatments have been intensifying in recent years. In this study, the non-human primate model of CD/NCGS, e.g., gluten-sensitive rhesus macaque, was utilized with the objective to evaluate the treatment potential of reduced gluten cereals using a reduced gluten (RG; 1% of normal gluten) barley mutant as a model. Conventional and RG barleys were used for the formulation of experimental chows and fed to gluten-sensitive (GS) and control macaques to determine if RG barley causes a remission of dietary gluten-induced clinical and immune responses in GS macaques. The impacts of the RG barley diet were compared with the impacts of the conventional barley-containing chow and the GFD. Although remission of the anti-gliadin antibody (AGA) serum responses and an improvement of clinical diarrhea were noted after switching the conventional to the RG barley diet, production of inflammatory cytokines, e.g., interferon-gamma (IFN-γ), tumor necrosis factor (TNF) and interleukin-8 (IL-8) by peripheral CD4+ T helper lymphocytes, persisted during the RG chow treatment and were partially abolished only upon re-administration of the GFD. It was concluded that the RG barley diet might be used for the partial improvement of gluten-induced disease but its therapeutic value still requires upgrading-by co-administration of additional treatments.

Topics: Animals; Antibodies; Celiac Disease; Cytokines; Diarrhea; Diet, Gluten-Free; Gliadin; Glutens; Hordeum; Immunity, Cellular; Immunity, Humoral; Inflammation; Interferon-gamma; Interleukin-8; Macaca mulatta; Malabsorption Syndromes; Mutation

In celiac disease (CD), gluten induces both adaptive and innate immune responses. Non-celiac gluten sensitivity (NCGS) is another form of gluten intolerance where the immune response is less characterized. The aim of our study was to explore and compare the early mucosal immunological events in CD and NCGS.. We challenged 30 HLA-DQ2(+) NCGS and 15 CD patients, all on a gluten-free diet, with four slices of gluten-containing bread daily for 3 days. Duodenal biopsy specimens were collected before and after challenge. The specimens were examined for cytokine mRNA by quantitative reverse transcriptase-PCR and for MxA-expression and CD3(+) intraepithelial lymphocytes (IELs) by immunohistochemistry and compared with specimens from untreated CD patients and disease controls.. In CD patients, tumor necrosis factor alpha (P=0.02) and interleukin 8 (P=0.002) mRNA increased after in vivo gluten challenge. The interferon gamma (IFN-γ) level of treated CD patients was high both before and after challenge and did not increase significantly (P=0.06). Four IFN-γ-related genes increased significantly. Treated and untreated CD patients had comparable levels of IFN-γ. Increased expression of MxA in treated CD patients after challenge suggested that IFN-α was activated on gluten challenge. In NCGS patients only IFN-γ increased significantly (P=0.03). mRNA for heat shock protein (Hsp) 27 or Hsp70 did not change in any of the groups. Importantly, we found that the density of IELs was higher in NCGS patients compared with disease controls, independent of challenge, although lower than the level for treated CD patients.. CD patients mounted a concomitant innate and adaptive immune response to gluten challenge. NCGS patients had increased density of intraepithelial CD3(+) T cells before challenge compared with disease controls and increased IFN-γ mRNA after challenge. Our results warrant further search for the pathogenic mechanisms for NCGS.

Topics: Adult; Aged; ATP Binding Cassette Transporter, Subfamily B, Member 2; ATP-Binding Cassette Transporters; Biopsy; Caspase 1; CD3 Complex; Celiac Disease; Diet, Gluten-Free; Duodenum; Female; Fluorescent Antibody Technique; Food Hypersensitivity; Glutens; Humans; Immunohistochemistry; Interferon-gamma; Interleukin-8; Intestinal Mucosa; Lymphocyte Count; Lymphocytes; Male; Middle Aged; Oxidoreductases Acting on Sulfur Group Donors; Proteasome Endopeptidase Complex; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; STAT1 Transcription Factor; T-Lymphocytes; Tumor Necrosis Factor-alpha; Up-Regulation

Less than one-tenth of the carriers of the risk genes HLA-DQ2 or HLA-DQ8 develop celiac disease, suggesting that other genetic and environmental factors are important in the pathogenesis. The role of gut microbiota has been addressed previously with inconsistent findings. Our aim was to evaluate microbiota, its receptors (Toll-like receptors [TLRs]), and regulators of the TLRs in the small intestinal mucosa in celiac disease.. Microbiota was analyzed by quantitative polymerase chain reaction (total bacteria and 10 bacterial group- and species-specific primers) and gene expression of interleukin-8 (IL-8), TLR2, TLR3, TLR4, TLR5, TLR9, and regulators of TLRs, Toll-interacting protein (TOLLIP), and single immunoglobulin IL-1R-related molecule, by relative quantitative reverse transcription-polymerase chain reaction in 10 children with celiac disease (untreated celiacs), 9 children with normal small intestinal mucosa (controls), and 6 adults with celiac disease with normal small intestinal mucosa after following a gluten-free diet (treated celiacs).. Small intestinal microbiota was comparable among controls, untreated celiacs, and treated celiacs. Expression of IL-8 mRNA, a marker of intestinal inflammation, was significantly increased in untreated celiacs as compared with treated celiacs (P=0.002) and controls (P=0.001). Expression of TLR-2 mRNA was significantly decreased in untreated (P=0.001) and treated (P=0.03) celiacs, whereas expression of TLR-9 mRNA was increased in untreated celiacs (P=0.001) as compared with controls. Expression of TOLLIP mRNA was downregulated in untreated celiacs as compared with controls (P=0.02).. Altered gene expression of TLR2, TLR9, and TOLLIP in small intestinal biopsies in celiac disease suggests that microbiota-associated factors may be important in the development of the disease.

Topics: Adolescent; Adult; Bacteria; Case-Control Studies; Celiac Disease; Child; Child, Preschool; Diet, Gluten-Free; Gene Expression Regulation; Humans; Inflammation; Interleukin-8; Intestinal Mucosa; Intestine, Small; Intracellular Signaling Peptides and Proteins; Metagenome; Middle Aged; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Toll-Like Receptor 2; Toll-Like Receptor 9

Dermatitis herpetiformis (DH) is an autoimmune blistering skin disease in which antigen presentation in the gastrointestinal mucosa results in cutaneous IgA deposition and distinct, neutrophil-driven cutaneous lesions. Our findings suggest that the qualitatively different immune response to gluten in the intestinal mucosa of patients with DH results in minimal clinical symptoms, allowing the continued ingestion of gluten and the eventual development of DH. Our model may provide a new way to understand the pathogenesis of other skin diseases associated with gastrointestinal inflammation such as pyoderma gangrenosum or erythema nodosum, or explain association of seronegative inflammatory arthritis with inflammatory bowel disease.

Topics: Animals; Celiac Disease; Dermatitis Herpetiformis; Diet, Gluten-Free; Humans; Immunity, Mucosal; Immunoglobulin A; Inflammation Mediators; Interleukin-8; Models, Biological; Skin; Tumor Necrosis Factor-alpha

Invasive techniques are still required to distinguish between uncomplicated and complicated forms of CD.. We set out to investigate the potential use of novel serum parameters, including IL-6, IL-8, IL-17, IL-22, sCD25, sCD27, granzyme-B, sMICA and sCTLA-4 in patients diagnosed with active CD, CD on a GFD, Refractory coeliac disease (RCD) type I and II, and enteropathy associated T-cell lymphoma (EATL).. In both active CD and RCDI-II elevated levels of the proinflammatory IL-8, IL-17 and sCD25 were observed. In addition, RCDII patients displayed higher serum levels of soluble granzyme-B and IL-6 in comparison to active CD patients. In contrast, no differences between RCDI and active CD or RCDII were observed. Furthermore, EATL patients displayed higher levels of IL-6 as compared to all other groups.. A series of novel serum parameters reveal distinctive immunological characteristics of RCDII and EATL in comparison to uncomplicated CD and RCDI.

Topics: Adult; Aged; Biomarkers; Celiac Disease; CTLA-4 Antigen; Cytokines; Diet, Gluten-Free; Enteropathy-Associated T-Cell Lymphoma; Granzymes; Histocompatibility Antigens Class I; Humans; Interleukin-17; Interleukin-2 Receptor alpha Subunit; Interleukin-22; Interleukin-6; Interleukin-8; Interleukins; Middle Aged; Retrospective Studies; ROC Curve; Severity of Illness Index; Statistics, Nonparametric; Tumor Necrosis Factor Receptor Superfamily, Member 7; Young Adult

The autoimmune enteropathy, coeliac disease (CD), is triggered by ingestion of gluten-containing grains. We recently reported that the chemokine receptor CXCR3 serves as a receptor for specific gliadin peptides that cause zonulin release and subsequent increase in intestinal permeability. To explore the role of CXCR3 in the immune response to gliadin, peripheral blood mononuclear cells from both patients with CD and healthy controls were incubated with either pepsin-trypsin-digested gliadin or 11 α-gliadin synthetic peptides in the presence or absence of a blocking anti-CXCR3 monoclonal antibody. Supernatants were analysed for interleukin-6 (IL-6), IL-8, IL-10, IL-13, IP-10 (CXCL10), tumour necrosis factor-α and interferon-γ. Gliadin broadly induced cytokine production irrespective of the clinical condition. However, IL-8 production occurred only in a subgroup of individuals and cells of the phagocytic lineage were the main source. Induction of IL-8 was reproduced by one of a comprehensive panel of synthetic α-gliadin peptides and was abrogated when CXCR3 was blocked before stimulation with either gliadin or this peptide in the CD group but not in the control group, suggesting that gliadin-induced IL-8 production was CXCR3-dependent gliadin induced IL-8 production only in CD.

Topics: Celiac Disease; Gliadin; Humans; Interleukin-8; Leukocytes, Mononuclear; Peptides; Receptors, CXCR3

The cytosolic phospolypase A(2) (cPLA(2)) - dependent release of arachidonic acid (AA) from the intra-epithelial lymphocytes plays a pivotal role in arming lymphocytes to cytolysis in the immune response of celiac disease. However, little is known about the role of enterocytes in releasing AA. Docosahexaenoic acid (DHA) is a long chain polyunsaturated fatty acid that counteracts many of the proinflammatory effect of AA. The aims of the present work were to evaluate if: 1) intestinal epithelial cells have a role in the celiac inflammation, releasing AA, and 2) if DHA is able to modulate the celiac inflammation, down-regulating the release of AA.. A human intestinal epithelial cell line (Caco-2) was exposed to gliadin peptides (PT-gl) (500 μg/ml) and DHA (2 μg/ml), both alone and simultaneously up to 24 h.. The exposure of those cells to PT-gl alone resulted in an increased AA release, cycloxygenase-2 expression, cPLA(2) activity and prostaglandin E(2) and interleukin-8 release in culture medium, whereas the simultaneous exposure of the cells to DHA and PT-gl prevented the above-mentioned increases.. These results suggest that intestinal epithelial cells sustain the celiac inflammation, releasing AA when stimulated with gliadin and that DHA inhibits the AA release by these cells.

Topics: Arachidonic Acid; Blotting, Western; Caco-2 Cells; Celiac Disease; Cyclooxygenase 2; Dinoprostone; Docosahexaenoic Acids; Down-Regulation; Epithelial Cells; Gliadin; Humans; Inflammation; Interleukin-8; Intestines; Peptide Fragments; Phospholipases A2, Cytosolic

To elucidate the role of innate immune responses in celiac disease, we investigated the effect of gliadin on blood monocytes from patients with celiac disease. Gliadin induced substantial TNF-alpha and IL-8 production by monocytes from patients with active celiac disease, lower levels by monocytes from patients with inactive celiac disease, and even lower levels by monocytes from healthy donors. In healthy donor monocytes gliadin induced IL-8 from monocytes expressing HLA-DQ2 and increased monocyte expression of the costimulatory molecules CD80 and CD86, the dendritic cell marker CD83, and the activation marker CD40. Gliadin also increased DNA binding activity of NF-kappaB p50 and p65 subunits in monocytes from celiac patients, and NF-kappaB inhibitors reduced both DNA binding activity and cytokine production. Thus, gliadin activation of HLA-DQ2(+) monocytes leading to chemokine and proinflammatory cytokine production may contribute to the host innate immune response in celiac disease.

Topics: Antigens, CD; B7-1 Antigen; B7-2 Antigen; CD40 Antigens; CD83 Antigen; Celiac Disease; Cytokines; Flow Cytometry; Gliadin; HLA-DQ Antigens; Humans; Immunoglobulins; Interleukin-8; Macrophage Activation; Membrane Glycoproteins; Monocytes; NF-kappa B; Peptide Fragments; Tumor Necrosis Factor-alpha

Patients with dermatitis herpetiformis (DH) have a gluten-sensitive enteropathy and while on gluten-containing diets have elevated levels of serum IL-8. We hypothesized that the mucosal immune response to gluten is responsible for the elevated serum IL-8. Six DH patients were studied while on a gluten-free diet (GFD), whereas four continued on a normal diet. Patients were followed for a mean 2.2 years and serum IL-8 was analyzed. Small bowel biopsies from five DH patients on normal diets, two DH patients on GFD, and six subjects with no small bowel abnormalities were analyzed for IL-8 mRNA. Serum IL-8 levels normalized in five of six patients on GFD and decreased in one, whereas serum IL-8 levels showed no statistically significant change in DH patients on normal diets. Small bowel biopsies from DH patients on normal diets had increased expression of IL-8 mRNA compared to normal subjects, whereas patients on a GFD showed no significant increase in small bowel mRNA. No significant IL-8 mRNA was detected in normal skin biopsies from patients with DH. These observations suggest that the IL-8 in the serum of patients with DH originates from the small bowel as a mucosal immune response to gluten ingestion.

Topics: Adult; Aged; Biopsy; Celiac Disease; Dermatitis Herpetiformis; Diet; Female; Glutens; Humans; Immunoglobulin A; Interleukin-8; Intestine, Small; Male; Middle Aged; RNA, Messenger

Celiac disease is an HLA-DQ2-associated disorder characterized by an intestinal T cell response. The disease-relevant T cells secrete IFN-gamma upon recognition of gluten peptides that have been deamidated in vivo by the enzyme tissue transglutaminase (transglutaminase 2 (TG2)). The celiac intestinal mucosa contains elevated numbers of mast cells, and increased histamine secretion has been reported in celiac patients. This appears paradoxical because histamine typically biases T cell responses in the direction of Th2 instead of the Th1 pattern seen in the celiac lesions. We report that histamine is an excellent substrate for TG2, and it can be efficiently conjugated to gluten peptides through TG2-mediated transamidation. Histamine-peptide conjugates do not exert agonistic effects on histamine receptors, and scavenging of biologically active histamine by gluten peptide conjugation can have physiological implications and may contribute to the mucosal IFN-gamma response in active disease. Interestingly, TG2 is able to hydrolyze the peptide-histamine conjugates when the concentrations of substrates are lowered, thereby releasing deamidated gluten peptides that are stimulatory to T cells.

Topics: Amino Acid Sequence; Celiac Disease; Cells, Cultured; Dendritic Cells; Epitopes, T-Lymphocyte; Free Radical Scavengers; Gliadin; Glutens; GTP-Binding Proteins; Histamine; Histamine Agonists; Histamine Antagonists; Humans; Hydrolysis; Interleukin-12; Interleukin-8; Molecular Sequence Data; Peptide Fragments; Protein Glutamine gamma Glutamyltransferase 2; Receptors, Histamine H1; Receptors, Histamine H2; Substrate Specificity; Transglutaminases

Activation of T cells in the intestinal mucosa in response to gluten exposure is thought to play a key role in the pathogenesis of coeliac disease. Moreover, the response of the rectal mucosa to gluten challenge has been considered a useful predictor of gluten sensitivity in coeliac disease. In the present study, we assessed early changes in the expression of proinflammatory cytokine genes and the T cell receptor (TCR) Vbeta repertoire in the rectal mucosa of coeliac disease patients following experimental gluten challenge. Cytokine gene expression was assessed in rectal mucosal biopsies from coeliac disease subjects and controls before and after rectal gluten challenge using quantitative reverse transcription polymerase chain reaction analysis, and the TCR Vbeta repertoire was characterized using a multiprobe RNase protection assay. Marked up-regulation of expression of the C-X-C chemokine IL-8, the proinflammatory cytokine IL-1beta, and the C-C chemokine monocyte chemotactic protein-1 occurred within 24 h of rectal gluten challenge in coeliac disease subjects, but not in controls. Furthermore, these changes occurred in the absence of parallel changes in the expressed repertoire of TCR Vbeta genes in the rectal mucosa. Thus, an increased expression of proinflammatory cytokine genes precedes the expansion of antigen-specific T cell populations in the early period following experimental exposure of the rectal mucosa of coeliac disease patients to gluten. These findings provide new insights into pathways that may be involved in the activation or reactivation of coeliac disease.

Topics: Administration, Rectal; Adult; Celiac Disease; Chemokine CCL2; Colon; Gene Expression; Glutens; Humans; Interleukin-1; Interleukin-8; Intestinal Mucosa; T-Lymphocytes; Up-Regulation