INT340797

Context Info Confidence 0.69 First Reported 2010 Last Reported 2010 Negated 1 Speculated 0 Reported most in Body Documents 1 Total Number 16 Disease Relevance 12.73 Pain Relevance 0.95

Anatomy Link Frequency T cells 8 corneal epithelium 6 blood 5 corneas 3 stroma 1 Btla (Mus musculus)

Pain Link Frequency Relevance Heat cytokine 128 93.12 Inflammation 240 90.16 Inflammatory response 16 43.28 corticosteroid 16 5.00 cINOD 16 5.00 imagery 16 5.00

Disease Link Frequency Relevance Heat Cold Sores 848 99.64 Sprains And Strains 96 99.24 Infection 624 98.84 Disease 128 96.96 Keratitis 592 95.40 Necrosis 16 93.32 Cancer 16 92.96 Hypersensitivity 320 91.80 INFLAMMATION 272 90.16 Death 16 87.60

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Immunohistochemistry results for BTLA expression in the corneas are shown in Figure 1D.

Positive_regulation (results) of Gene_expression (expression) of BTLA in corneas

1) Confidence 0.69 Published 2010 Journal Molecular Vision Section Body Doc Link PMC2965573 Disease Relevance 1.05 Pain Relevance 0.07

However, BTLA expression did not increase in CD8+ T cells after HSV-1 infection (Figure 1C).

Neg (not) Positive_regulation (increase) of Gene_expression (expression) of BTLA in T cells associated with cold sores and infection

2) Confidence 0.69 Published 2010 Journal Molecular Vision Section Body Doc Link PMC2965573 Disease Relevance 1.06 Pain Relevance 0.07

BTLA expression is upregulated in the murine peripheral blood and cornea after HSV-1 infection

Positive_regulation (upregulated) of in cornea Gene_expression (expression) of BTLA in blood associated with cold sores and infection

3) Confidence 0.60 Published 2010 Journal Molecular Vision Section Body Doc Link PMC2965573 Disease Relevance 0.80 Pain Relevance 0.05

The recombinant pBTLA was transfected into the HEK293 cell line (the Institute of Genetics of Fudan University, Shanghai, China) to express the target protein BTLA, which was detected by indirect immunofluorescence and western blotting.

Positive_regulation (transfected) of Gene_expression (transfected) of pBTLA

4) Confidence 0.60 Published 2010 Journal Molecular Vision Section Body Doc Link PMC2965573 Disease Relevance 0 Pain Relevance 0

However, in corneal tissues derived from HSV-1 infected mice, BTLA expression was increased in the corneal epithelium, stroma, and endothelium (Figure 1E).

Positive_regulation (increased) of Gene_expression (expression) of BTLA in corneal epithelium associated with cold sores

5) Confidence 0.60 Published 2010 Journal Molecular Vision Section Body Doc Link PMC2965573 Disease Relevance 1.01 Pain Relevance 0.07

BTLA expression increased in CD4+ T cells, peaking on day 10 after infection (Figure 1A).

Positive_regulation (increased) of Gene_expression (expression) of BTLA in T cells associated with infection

6) Confidence 0.60 Published 2010 Journal Molecular Vision Section Body Doc Link PMC2965573 Disease Relevance 0.93 Pain Relevance 0.04

In the normal uninfected mouse cornea, BTLA expression was only detected in the corneal epithelium (Figure 1D).

Positive_regulation (detected) of Gene_expression (expression) of BTLA in corneal epithelium

7) Confidence 0.46 Published 2010 Journal Molecular Vision Section Body Doc Link PMC2965573 Disease Relevance 1.03 Pain Relevance 0.07

BTLA is constitutively expressed by naïve CD4+ and CD8+ T cells and is further upregulated upon T cell activation [15].

Positive_regulation (upregulated) of in T cell Gene_expression (expressed) of BTLA in T cells

8) Confidence 0.46 Published 2010 Journal Molecular Vision Section Body Doc Link PMC2965573 Disease Relevance 0.72 Pain Relevance 0.15

Our findings demonstrate that infection of BALB/c mice with HSV-1 KOS strain by corneal scarification resulted in upregulation of BTLA expression in the infected corneas and in CD4+ T cells from murine peripheral blood.

Positive_regulation (upregulation) of Gene_expression (expression) of BTLA in blood associated with cold sores, sprains and strains and infection

9) Confidence 0.46 Published 2010 Journal Molecular Vision Section Body Doc Link PMC2965573 Disease Relevance 1.55 Pain Relevance 0.17

As shown in Figure 3A, at 48 h post-transfection, the immunofluorescence intensity was high in HEK293 cells transfected with pBTLA.

Positive_regulation (transfected) of Gene_expression (transfected) of pBTLA

10) Confidence 0.44 Published 2010 Journal Molecular Vision Section Body Doc Link PMC2965573 Disease Relevance 0.49 Pain Relevance 0.04

Cells were transfected with the recombinant pBTLA or the empty vector pcDNA3.1 using Lipofectamine 2000 reagent (Invitrogen) according to the manufacturer's instructions.

Positive_regulation (transfected) of Gene_expression (transfected) of pBTLA

11) Confidence 0.44 Published 2010 Journal Molecular Vision Section Body Doc Link PMC2965573 Disease Relevance 0 Pain Relevance 0

The recombinant pBTLA was transfected into the HEK293 cell line (the Institute of Genetics of Fudan University, Shanghai, China) to express the target protein BTLA, which was detected by indirect immunofluorescence and western blotting.

Positive_regulation (transfected) of Gene_expression (express) of BTLA

12) Confidence 0.40 Published 2010 Journal Molecular Vision Section Body Doc Link PMC2965573 Disease Relevance 0 Pain Relevance 0

BTLA expression increased both in the corneas of HSV-1 infected mice and in CD4+ T cells in the murine peripheral blood.

Positive_regulation (increased) of Gene_expression (expression) of BTLA in T cells associated with cold sores

13) Confidence 0.40 Published 2010 Journal Molecular Vision Section Abstract Doc Link PMC2965573 Disease Relevance 1.26 Pain Relevance 0.05

BTLA expression is upregulated in the murine peripheral blood and cornea after HSV-1 infection

Positive_regulation (upregulated) of Gene_expression (expression) of BTLA in blood associated with cold sores and infection

14) Confidence 0.21 Published 2010 Journal Molecular Vision Section Body Doc Link PMC2965573 Disease Relevance 0.80 Pain Relevance 0.05

However, in corneal tissues derived from HSV-1 infected mice, BTLA expression was increased in the corneal epithelium, stroma, and endothelium (Figure 1E).

Positive_regulation (increased) of in endothelium Gene_expression (expression) of BTLA in corneal epithelium associated with cold sores

15) Confidence 0.21 Published 2010 Journal Molecular Vision Section Body Doc Link PMC2965573 Disease Relevance 1.01 Pain Relevance 0.07

However, in corneal tissues derived from HSV-1 infected mice, BTLA expression was increased in the corneal epithelium, stroma, and endothelium (Figure 1E).

Positive_regulation (increased) of in stroma Gene_expression (expression) of BTLA in corneal epithelium associated with cold sores

16) Confidence 0.21 Published 2010 Journal Molecular Vision Section Body Doc Link PMC2965573 Disease Relevance 1.01 Pain Relevance 0.07

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