Chronic HIV infection is associated with upregulation of proinflammatory cytokine and chemokine and alpha defensin gene expression in colorectal mucosa

Jennifer Mait-Kaufman, Esra Fakioglu, Pedro M M Mesquita, Julie Elliott, Yungtai Lo, Rebecca Pellett Madan

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)615-622
Number of pages8
JournalAIDS Research and Human Retroviruses
Volume31
Issue number6
DOIs
StatePublished - Jun 1 2015

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alpha-Defensins
Chemokines
HIV Infections
Mucous Membrane
Up-Regulation
HIV
Ulcerative Colitis
Cytokines
Gene Expression
Messenger RNA
Viral Load
Interleukin-8
Biopsy
Real-Time Polymerase Chain Reaction
Interleukin-6
HIV Long Terminal Repeat
Inflammation
Defensins
Toll-Like Receptors
Down-Regulation

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Infectious Diseases

Cite this

Chronic HIV infection is associated with upregulation of proinflammatory cytokine and chemokine and alpha defensin gene expression in colorectal mucosa. / Mait-Kaufman, Jennifer; Fakioglu, Esra; Mesquita, Pedro M M; Elliott, Julie; Lo, Yungtai; Madan, Rebecca Pellett.

In: AIDS Research and Human Retroviruses, Vol. 31, No. 6, 01.06.2015, p. 615-622.

Research output: Contribution to journalArticle

Mait-Kaufman, Jennifer ; Fakioglu, Esra ; Mesquita, Pedro M M ; Elliott, Julie ; Lo, Yungtai ; Madan, Rebecca Pellett. / Chronic HIV infection is associated with upregulation of proinflammatory cytokine and chemokine and alpha defensin gene expression in colorectal mucosa. In: AIDS Research and Human Retroviruses. 2015 ; Vol. 31, No. 6. pp. 615-622.
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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.",
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