Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022568 (keratitis)
 5,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The most common viral disease of cats worldwide is the infection with feline herpesvirus 1 (FeHV-1). This infection may be followed by Herpetic stromal keratitis (HSK), which is supposed to have an immunopathological basis. Experiments using herpes simplex viruses (HSV) in mouse models indicated that HSK may be treated by topical application of the interleukin 10 (IL-10) gene. The objective of this study was the construction of human herpes simplex virus type 1 (HSV-1)-based amplicon vectors expressing feline interleukin genes and delivery of these genes into cells of feline origin. HSV-1-based amplicon vectors encoding either the enhanced green fluorescent protein, the feline IL-6 or the feline IL-10 under control of the HSV-1 immediate-early 4/5 promotor were constructed, packaged into amplicon particles, transduced into feline cells, and tested for RNA synthesis and biological activity. Feline cells were successfully transduced by HSV-1-based amplicon particles and RNA specific for the transgene was detected already at 2h post transduction, with a maximum at 24h. The recombinant feline IL-10 was functionally active as demonstrated by the reduction of both IL-12 p40 and interferon-gamma-mRNA production in Pansorbin stimulated feline peripheral mononuclear cells. Similarly, the recombinant feline IL-6, which was secreted into the supernatant of transduced cells, was able to support the growth of the IL-6-dependent murine B cell hybridoma 7TD1. HSV-1-based amplicon particles are able to transduce cells of feline origin with genes encoding biologically functional feline IL-10 or IL-6. It will be of high interest to study the effects of these tools in vivo.
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PMID:HSV-1-based amplicon particles are able to transduce cells of feline origin with genes encoding biologically functional feline IL-10 or IL-6. 1188 94

PURPOSE. Interleukin (IL)-12p40 can couple with IL-12p35 or p19 chains to form the molecules IL-12p70 and IL-23, respectively, which promote T(H)1 cytokine responses. IL-12p35 can bind to EBI3 to form the anti-inflammatory molecule IL-35, but a proinflammatory function of IL-12p35 independent of IL-12p40 has not been described. Here such a function in a mouse model of herpes stromal keratitis (HSK), a CD4(+) T(H)1 cell-dependent corneal inflammation, is demonstrated. METHODS. Corneas of wild-type (WT), IL-12p40(-/-), IL-12p35(-/-), and IL-12p35(-/-)p40(-/-) (double knockout) mice were infected with the RE strain of HSV-1, and HSK was monitored based on corneal opacity, neovascularization, leukocytic infiltrate, and cytokine/chemokine levels. RESULTS. All mouse strains developed moderate HSK by 11 days after infection (dpi). However, from 11 to 21 dpi, HSK progressed in WT and IL-12p40(-/-) mice but regressed in IL-12p35(-/-) and IL-12p35(-/-)p40(-/-) mice. HSK regression was characterized by reductions in neutrophils and CD4(+) T cells and attenuation of blood vessels, which was associated with reduced levels of the chemokines KC (CXCL3), Mip-2 (CXCL2), and MCP-1 (CCL2) and the angiogenic factor vascular endothelial growth factor. CONCLUSIONS. HSK development does not require IL-12p40 and is thus independent of IL-12p70 and IL-23. However, late HSK progression does require a previously unrecognized IL-12p40-independent, proinflammatory function of IL-12p35.
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PMID:A novel p40-independent function of IL-12p35 is required for progression and maintenance of herpes stromal keratitis. 2020 59