13 research outputs found
Idiopathic pulmonary fibrosis is strongly associated with productive infection by herpesvirus saimiri
Idiopathic pulmonary fibrosis is a fatal disease without effective therapy or diagnostic test. To investigate a
potential role for c�herpesviruses in this disease, 21 paraffin-embedded lung biopsies from patients diagnosed
with idiopathic pulmonary fibrosis and 21 lung biopsies from age-matched controls with pulmonary fibrosis of
known etiology were examined for a series of c�herpesviruses’ DNA/RNA and related proteins using in situ
hybridization and reverse transcriptase-polymerase chain reaction (RT-PCR)-based methods. We detected four
proteins known to be in the genome of several c�herpesviruses (cyclin D, thymidylate synthase, dihydrofolate
reductase, and interleukin-17) that were strongly co-expressed in the regenerating epithelial cells of each of the
21 idiopathic pulmonary fibrosis cases and not in the benign epithelia of the controls. Among the c�
herpesviruses, only herpesvirus saimiri expresses all four of these ‘pirated’ mammalian proteins. We found
herpesvirus saimiri DNA in the regenerating epithelial cells of 21/21 idiopathic pulmonary fibrosis cases using
four separate probe sets but not in the 21 controls. RT-PCR showed that the source of the cyclin D RNA in active
idiopathic pulmonary fibrosis was herpesvirus saimiri and not human. We cloned and sequenced part of
genome corresponding to the DNA polymerase herpesvirus saimiri gene from an idiopathic pulmonary fibrosis
sample and it matched 100% with the published viral sequence. These data are consistent with idiopathic
pulmonary fibrosis representing herpesvirus saimiri-induced pulmonary fibrosis. Thus, treatment directed
against viral proliferation and/or viral-associated proteins may halt disease progression. Further, demonstration
of the viral nucleic acids or proteins may help diagnose the disease
Amelioration of immune-mediated experimental colitis: tolerance induction in the presence of pre-existing immunity and surrogate antigen bystander effect
ABSTRACT Oral tolerance is a recognized procedure for induction of antigen-specific peripheral immune hyporesponsiveness. Recently, it has been shown that oral tolerance can be used to prevent experimental colitis. The aim of this study was to test whether induction of oral tolerance toward proteins extracted from inflammatory and noninflammatory colons can alleviate preexisting experimental colitis. Colitis was induced in BALB/c mice by intracolonic instillation of 2,4,6-trinitrobenzenesulfonic acid (TNBS). Mice received five oral doses of colonic proteins extracted from TNBS-induced colitis or normal colons, before, or 7 days after colitis was induced. Standard clinical, macroscopic, and microscopic scores were used for colitis assessment. Serum interferon ␥ (IFN␥) and interleukin (IL)4 levels were measured by enzyme-linked immunosorbent assay. Feeding of colitis-or normal colon-extracted proteins before, or following colitis induction, ameliorated colonic inflammation as shown by decreased diarrhea, increased body weight, reduction of colonic ulcerations, intestinal and peritoneal adhesions, wall thickness, and edema. Histological parameters for colitis were markedly improved in tolerized animals, and there was a significant reduction in inflammatory response and mucosal ulcerations. Tolerized mice developed an increase in IL4 and a decrease in IFN␥ serum levels. The results show that induction of oral tolerance to colitis-or normal colon-extracted proteins down-regulated preexisting anticolon immune response, thereby ameliorating experimental colitis. Tolerance induction was mediated via a shift from a proinflammatory T helper (Th)1 to an anti-inflammatory Th2 immune response
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