title: Characteristic changes in microbial community composition and expression of innate immune genes in acute appendicitis.
abstract: Appendicitis represents a common and severe gastrointestinal illness in younger individuals worldwide. The disease is characterized by an excessive inflammatory response and it is believed that bacterial overgrowth due to blockage of the appendix lumen might be involved. Despite the high incidence, only limited data on the pathophysiological changes exist; in particular, the innate immune responses involved are largely unknown. Real-time PCR analysis of tissue samples from inflamed and normal appendices demonstrated differentially regulated expression patterns of epithelial-derived antimicrobial peptides (AMP). The α-defensins human neutrophil peptides 1-3, HD5 and HD6, as well as the two β-defensins, human β-defensins (hBD)-2 and hBD-3, were up-regulated, whereas hBD-1 was down-regulated in acute appendicitis. Expression of upstream regulators of AMP expression, NOD-2 and TLRs 1, 2, 4, 5, 7, 8 and 10 was significantly increased as detected by real-time PCR. Finally, we confirmed the involvement of the pro-inflammatory cytokines IL-1β and IL-8, and detected characteristic changes in microbial community composition in appendicitis tissue specimens by 16S rDNA based detection techniques. In this study, we demonstrate a differential regulation of the innate immune system along with an altered bacterial diversity in acute appendicitis.
authors: Department of Internal Medicine I, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany aarlt@1med.uni-kiel.de.
authors: Alexander
authors: A
authors: Arlt
authors: Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors: Richa
authors: R
authors: Bharti
authors: Department of Surgery and Psychiatry, University Hospital of Kuopio, Kuopio, Finland.
authors: Imre
authors: I
authors: Ilves
authors: Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors: Robert
authors: R
authors: Häsler
authors: Department of Surgery and Psychiatry, University Hospital of Kuopio, Kuopio, Finland.
authors: Pekka
authors: P
authors: Miettinen
authors: Department of Surgery and Psychiatry, University Hospital of Kuopio, Kuopio, Finland.
authors: Hannu
authors: H
authors: Paajanen
authors: Department of Internal Medicine I, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors: Gabriele
authors: G
authors: Brunke
authors: Department of Internal Medicine I, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors: Mark
authors: M
authors: Ellrichmann
authors: Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany Department of Environmental Health Sciences, University Medical Center, Freiburg, Germany.
authors: Ateequr
authors: A
authors: Rehman
authors: Department of Surgery, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors: Charlotte
authors: C
authors: Hauser
authors: Department of Surgery, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors: Jan-Hendrik
authors: JH
authors: Egberts
authors: Department of Internal Medicine I, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany Department of Surgery and Psychiatry, University Hospital of Kuopio, Kuopio, Finland.
authors: Stephan J
authors: SJ
authors: Ott
authors: Department of Internal Medicine I, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany Department of Surgery and Psychiatry, University Hospital of Kuopio, Kuopio, Finland.
authors: Stefan
authors: S
authors: Schreiber
authors: Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors: Philip
authors: P
authors: Rosenstiel
authors: Department of Internal Medicine I, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany Department of Surgery and Psychiatry, University Hospital of Kuopio, Kuopio, Finland Institute of Biomedicine, Department of Physiology and Biocenter Oulu, University of Oulu, Oulu, Finland.
authors: Karl-Heinz
authors: KH
authors: Herzig
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D001064:Appendicitis / Q000235:genetics* / Q000382:microbiology*; D001419:Bacteria / Q000145:classification / Q000276:immunology; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D023082:Defensins / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010455:Peptides / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D055815:Young Adult
chemical_list: D018076:DNA, Complementary; D023082:Defensins; D010455:Peptides; D012333:RNA, Messenger; D012336:RNA, Ribosomal, 16S
keywords: Antimicrobial peptides; appendicitis; defensins; inflammation; innate immunity; microbial community