title: Chronic HIV Infection Is Associated with Upregulation of Proinflammatory Cytokine and Chemokine and Alpha Defensin Gene Expression in Colorectal Mucosa.
abstract: HIV may induce gastrointestinal (GI) mucosal immune dysregulation similar to inflammation observed in ulcerative colitis (UC). Colorectal biopsies from healthy controls (N=12) and from participants with HIV (N=20) or UC (N=9) were subjected to real time (RT)-PCR for selected cytokines, chemokines, antimicrobial peptides, Toll-like receptors, and inflammatory signaling and epithelial barrier proteins. HIV long terminal repeat relative copy number (RCN) in HIV participant biopsies was quantified by RT-PCR. Mean interleukin (IL)-6 mRNA levels did not differ significantly between HIV and UC participants (p=0.48) but were significantly higher relative to control mRNA levels only for HIV participants (p=0.03). Mean IL-8 and human defensin (HD) 5 mRNA levels were similar between HIV and UC participants (p=1.0 and p=0.35, respectively) and were significantly greater in both groups relative to controls (p<0.05 for all). Human beta-defensin (HBD)-2 mRNA levels were higher in UC relative to HIV and control participants (p<0.01 for both). Conversely, HBD-1 mRNA levels were downregulated in UC vs. HIV participants (p=0.01). Mediator gene expression did not differ significantly between HIV participants with detectable (N=10) or nondetectable (N=10) plasma viral loads. Tissue HIV relative copy number (RCN) correlated with plasma viral load (r=0.88, p<0.01) but not with mediator mRNA levels. The results of this study indicate that both chronic HIV infection and UC are associated with similar patterns of IL-6, IL- 8, and HD5 expression in colorectal biopsy tissue. These findings suggest overlapping mechanisms for GI mucosal inflammation in these two illnesses and merit further investigation in larger studies.
authors.affiliation: 1Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Mait-Kaufman
authors.affiliation: 1Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Esra
authors.initials: E
authors.lastname: Fakioglu
authors.affiliation: 1Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York.|2Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Pedro M M
authors.initials: PM
authors.lastname: Mesquita
authors.affiliation: 3Center for Prevention Research in the Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
authors.forename: Julie
authors.initials: J
authors.lastname: Elliott
authors.affiliation: 4Department of Epidemiology and Public Health, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Yungtai
authors.initials: Y
authors.lastname: Lo
authors.affiliation: 1Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Rebecca Pellett
authors.initials: RP
authors.lastname: Madan
mesh_terms: D000328:Adult; D001706:Biopsy; D002908:Chronic Disease; D003106:Colon / Q000473:pathology*; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D012007:Rectum / Q000473:pathology*; D015854:Up-Regulation; D023084:alpha-Defensins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D016207:Cytokines; D023084:alpha-Defensins