Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin-17 (IL-17) is a prototype member of a new cytokine family with six species identified to date. IL-17 is secreted mainly by activated CD4(+) and CD8(+) T lymphocytes, while its receptor is distributed ubiquitously. IL-17 has been classified as a proinflammatory cytokine because of its ability to induce the expression of many mediators of inflammation, most strikingly those that are involved in the proliferation, maturation and chemotaxis of neutrophils. Increased levels of IL-17 have been associated with several conditions, including airway inflammation, rheumatoid arthritis, intraperitoneal abscesses and adhesions, inflammatory bowel disease, allograft rejection, psoriasis, cancer and multiple sclerosis. This review provides an overview of IL-17 activities, concentrating on those that lead to neutrophil recruitment.
Cell Mol Life Sci 2004 Mar
PMID:Interleukin-17: a mediator of inflammatory responses. 1500 96

Recent studies have suggested that probiotics or short chain fatty acids (SCFAs) exert a therapeutic effect on inflammatory bowel disease (IBD) patients. In a previous study, we demonstrated that Clostridium butyricum produces high levels of SCFAs in culture. In addition, a yogurt-based additive effectively masked, completely eliminating the unpleasant odor derived from the SCFAs. We recently reported that the oral administration of both high and low dose diets (50% w/w for 17 days and 5% w/w for 16 months, respectively) of the Clostridium butyricum derivative did not cause pathological abnormalities in rats. In the present study, we evaluated the effects of this product against dextran sulfate sodium (DSS)-induced experimental colitis in rats. Five-week-old male Wistar Hannover GALAS rats were given a mixture of a standard diet containing 3% (w/w) of DSS for 8 days. In the derivative-fed group, Clostridium butyricum derivative (20% w/w) with 0.1% (w/w) additive was also added to their diet. The control-fed group was given tap water (20% w/w) with 0.1% (w/w) additive. After 8 days, a laparotomy was performed, and macroscopic and microscopic inflammation scoring was determined. The Clostridium butyricum derivative effectively prevented bloody diarrhea. In addition, mucosal damage to the derivative-fed group was significantly reduced macroscopically compared to that of the control-fed group. The potential clinical efficacy of the Clostridium butyricum derivative in IBD patients is also discussed.
Int J Mol Med 2004 Apr
PMID:Clostridium butyricum, a probiotic derivative, suppresses dextran sulfate sodium-induced experimental colitis in rats. 1501 Aug 59

This review summarizes the complex role of heat-shock proteins (Hsp) in immune reactions, especially the cellular effects of heat-shock proteins during the recognition processes by innate immunity. The role of heat-shock proteins in the pathogenesis of two multifactorial diseases, i.e. inflammatory bowel disease (IBD) and atherosclerosis is highlighted. A new hypothesis on "immunodeficiency burden" is presented. According to this hypothesis, susceptibility to any multifactorial disease in any given subject and in the presence of specific environmental factors is the aggregate effect of polymorphisms resulting in the failure of protective immunity with consequent disease.
Mol Immunol 2004 May
PMID:Immunological aspects of heat-shock proteins-the optimum stress of life. 1514 May 73

Nuclear factor-kappaB (NF-kappaB) is a major transcription factor that plays an essential role in several aspects of human health including the development of innate and adaptive immunity. The dysregulation of NF-kappaB is associated with many disease states such as AIDS, atherosclerosis, asthma, arthritis, cancer, diabetes, inflammatory bowel disease, muscular dystrophy, stroke, and viral infections. Recent evidence also suggests that the dysfunction of NF-kappaB is a major mediator of some human genetic disorders. Appropriate regulation and control of NF-kappaB activity, which can be achieved by gene modification or pharmacological strategies, would provide a potential approach for the management of NF-kappaB related human diseases. This review summarizes the current knowledge of the physiological and pathophysiological functions of NF-kappaB and its possible role as a target of therapeutic intervention
J Mol Med (Berl) 2004 Jul
PMID:Nuclear factor-kappaB: its role in health and disease. 1517 63

The immunomodulatory and anti-inflammatory effects of thalidomide are associated with inhibition of TNF-alpha levels. However, the mechanism by which thalidomide reduces TNF-alpha production remains elusive. NF-kappaB is known to play a central role in regulating inflammatory responses in patients with inflammatory bowel disease (IBD). We tested whether thalidomide acts through inhibiting NF-kappaB activity. HT-29 cells were stimulated with LPS (1 microg/ml) alone, or after pretreatment with thalidomide (100 microg/ml), and NF-kappaB activity was determined by gel mobility shift assays. RT-PCR was used to measure expression of the proinflammatory cytokine genes TNF-alpha, IL-1beta and IL-8. The level of TNF-alpha mRNA was also analyzed by real-time quantitative RT-PCR, and TNF-alpha protein was measured by ELISA. Thalidomide pretreatment did not affect NF-kappaB activity in HT-29 cells stimulated with LPS but production of TNF-alpha was depressed. Thalidomide was found to accelerate the degradation of TNF-alpha mRNA, but had little effect on IL-1beta or IL-8. These observations suggest that the immunomodulatory effect of thalidomide in colonic epithelial cells is associated with inhibition of TNF-alpha. However, it does not act by inhibiting NF-kappaB but rather by inducing degradation of TNF-alpha mRNA.
Mol Cells 2004 Apr 30
PMID:The effects of thalidomide on the stimulation of NF-kappaB activity and TNF-alpha production by lipopolysaccharide in a human colonic epithelial cell line. 1517 32

Etiopathogenesis of mucosal inflammation in inflammatory bowel disease remains a complex and enigmatic field; various factors (genetic, environmental and microbial) trigger an event that activates intestinal immune and nonimmune systems culminating in inflammation and tissue injury. Specifically, both innate and adaptive immune systems seem to play important roles in the pathophysiology of this disease. Cyclosporine A represents a macrolide immune modulator with primary inhibitory effects on T helper lymphocyte production of interleukin-2, and other cytokines leading to altered T-lymphocyte and B-lymphocyte function. The diversity of its therapeutic outcome reported in inflammatory bowel disease may be due to the intricate immuno-pathogenic profile of the disease and the variety of the applied dose-dependent courses of therapy. Cyclosporine A exerts additional actions on other components of the inflammatory infiltrate, including neutrophils and mast cells, thereby appearing to be a multi-dynamic therapeutic approach, although with potential drawbacks, that may be applied alone or combined with other immunomodulatory agents in inflammatory bowel disease patients. Because cyclosporine A induces apoptosis of T-lymphocytes responsible for perpetuation of the chronic inflammatory process in the disease with potential tumorigenic effect, it may exert a further inhibitory effect on cancer development in inflammatory bowel disease patients, and can be combined with other relative agents, such as rapamycin, which also promotes T-lymphocyte apoptosis. Therefore, recently established multifactorial action of cyclosporine A in relation to the pathogenesis of the disease can open new horizons for prospective, controlled trials in large cohorts, aiming to emphasize cyclosporine A's potential.
J Cell Mol Med
PMID:Immunomodulatory benefits of cyclosporine A in inflammatory bowel disease. 1549 7

Crohn's disease is associated with increased permeability of the intestinal barrier even in quiescent patients. Increased intestinal permeability may cause dysregulated immunological responses in the intestinal mucosa that leads to chronic intestinal inflammation. We have studied the expression of tight junction proteins (occludin and zonula occludens), alpha2-smooth muscle actin, TGF-beta with a cytoskeletal protein (F-actin) in the intestinal epithelium of patients with inflammatory bowel disease. Surgical samples were obtained from 6 controls (individuals without inflammatory bowel disease), 8 patients with ulcerative colitis and 7 patients with Crohn's disease. F-actin was visualized with fluorescein phalloidin. Tight junction proteins, alpha2 smooth muscle actin, and TGFbeta were visualized by the immunofluorescent method. Occludin and zonula occludens found in apical tight junctions in normal epithelium were dislocated to the basolateral position and in the lamina propria extracellular matrix in patients with Crohn's disease, while the structure of F-actin was maintained in inactive or minimally inflamed mucosa. TGF-beta positive inflammatory cells were increased in ulcerative colitis and Crohn's disease mucosa. Subepithelial myofibroblasts were constitutively found in controls, ulcerative colitis, and Crohn's disease mucosa. Latent dislocation of tight junction proteins, without disturbance of the cytoskeleton in the inactive mucosa of patients with Crohn's disease, may permit the invasion of gut antigens because the functional disruption of tight junctions could initiate an altered immune response.
Int J Mol Med 2005 Mar
PMID:Dislocation of tight junction proteins without F-actin disruption in inactive Crohn's disease. 1570 29

The etiology of ulcerative colitis (UC) is not known. Recent studies support a primary role of the appendix in the pathogenesis of UC, however phenotypical studies of proliferating cells in the appendix have not been reported. We report phenotypical studies of lymphocytes and of proliferating subpopulations in the appendix of patients with inflammatory bowel disease and of controls. Surgical samples of the appendix were obtained from 5 patients with colon cancer, 5 with acute appendicitis, 12 with UC and 7 with Crohn's disease (CD). Frozen sections were cut from fixed samples, and immunostained with lymphocyte markers and anti-Ki-67 antibodies. The number of Ki-67(+) proliferating cells, CD19, and CD138 cells was significantly higher in the appendix of patients with UC than in controls, patients with acute appendicitis, and patients with CD. Immunohistological double staining revealed significant proliferation of CD3, CD19, and CD138 cells in the appendix of patients with UC. The proportions of Ki-67(+) cells in CD3, CD19, and CD138 cells were significantly higher in both total UC patients and patients in remission-stage UC, than in controls, patients with acute appendicitis, and patients with CD. Lamina propria cells in the appendix of patients with UC showed augmented proliferation with increased numbers of CD19 and CD138 cells. The number of CD3 cells was not significantly increased, but the proportion of proliferating CD3 cells was increased. An increased proportion of Ki-67(+) cells in CD19 and CD138 cells represents proliferation of immature plasma cells in the appendix of patients with UC, and proliferation of such immature plasma cells was seen in both active- and remission-stage UC. Proliferation of immature plasma cells in the appendix of patients with UC suggests a primary role of humoral immune responses in the pathogenesis of UC.
Int J Mol Med 2005 Mar
PMID:Significance of increased proliferation of immature plasma cells in the appendix of patients with ulcerative colitis. 1570 31

Asthma is a familial inflammatory disease of the airways of the lung. Microbial exposures in childhood protect against asthma through unknown mechanisms. The innate immune system is able to identify microbial components through a variety of pattern-recognition receptors (PRRs). NOD1 is an intracellular PRR that initiates inflammation in response to bacterial diaminopimelic acid (iE-DAP). The NOD1 gene is on chromosome 7p14, in a region that has been genetically linked to asthma. We carried out a systematic search for polymorphism in the gene. We found an insertion-deletion polymorphism (ND(1)+32656) near the beginning of intron IX that accounted for approximately 7% of the variation in IgE in two panels of families (P<0.0005 in each). Allele*2 (the insertion) was associated with high IgE levels. The same allele was strongly associated with asthma in an independent study of 600 asthmatic children and 1194 super-normal controls [odds ratio (OR) 6.3; 95% confidence interval (CI) 1.4-28.3, dominant model]. Differential binding of the two ND(1)+32656 alleles was observed to a protein from nuclei of the Calu 3 epithelial cell line. In an accompanying study, the deletion allele (ND(1)+32656*1) was found to be associated with inflammatory bowel disease. The results indicate that intracellular recognition of specific bacterial products affects the presence of childhood asthma.
Hum Mol Genet 2005 Apr 01
PMID:NOD1 variation, immunoglobulin E and asthma. 1571 49

The identification of the role of genetic variants within NOD2 (CARD15) in Crohn's disease and ulcerative colitis susceptibility highlight the role of the innate immune system in inflammatory bowel disease (IBD) pathogenesis. NOD1 (CARD4) is located on chromosome 7p14.3, in a region of known linkage to IBD and encodes an intracellular bacterial pathogen-associated molecular pattern receptor that is closely related to NOD2. We have identified strong association between haplotypes in the terminal exons of NOD1 and IBD (multi-allelic P = 0.0000003) in a panel of 556 IBD trios. The deletion allele of a complex functional NOD1 indel polymorphism (ND(1) + 32656*1) was significantly associated with early-onset IBD (P = 0.0003) in unrelated cases and controls. ND1 + 32656*1 was also associated with extra-intestinal manifestations of IBD (P = 0.04). These findings in two independent populations provide strong evidence for a role for NOD1 variants in IBD susceptibility and reinforce the role of the innate immune system in IBD pathogenesis.
Hum Mol Genet 2005 May 15
PMID:Association between a complex insertion/deletion polymorphism in NOD1 (CARD4) and susceptibility to inflammatory bowel disease. 1579 May 94


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