INT90792

Context Info Confidence 0.80 First Reported 2000 Last Reported 2011 Negated 2 Speculated 1 Reported most in Body Documents 144 Total Number 146 Disease Relevance 87.88 Pain Relevance 30.03

extracellular space (Il10) extracellular region (Il10) intracellular (Il10)

Anatomy Link Frequency T cells 16 B cells 10 macrophages 9 A20 4 dendritic cells 3 Il10 (Mus musculus)

Pain Link Frequency Relevance Heat cytokine 2694 100.00 Inflammation 2024 100.00 Inflammatory response 197 100.00 Spinal cord 155 99.98 agonist 77 99.82 Inflammatory mediators 48 99.68 Sciatic nerve 119 99.50 adenocard 228 99.48 dexamethasone 41 99.38 ischemia 57 99.04

Disease Link Frequency Relevance Heat INFLAMMATION 2251 100.00 Targeted Disruption 488 99.96 Cytomegalovirus Infection 299 99.84 Reperfusion Injury 19 99.80 Apoptosis 818 99.54 Infection 2442 99.52 Obesity 178 99.48 Chlamydia Infection 360 99.44 Immunization 192 99.44 Sprains And Strains 876 99.38

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

MAIN OUTCOME MEASURE(S): Microscopic evaluation to assess the presence and localization of IL-10 throughout the menstrual cycle in both eutopic endometrial and adenomyotic tissues of women with adenomyosis and compare it with IL-10 expression in the normal endometrium.

Localization (localization) of IL-10 in endometrium

1) Confidence 0.80 Published 2009 Journal Fertil. Steril. Section Body Doc Link 18439592 Disease Relevance 0.08 Pain Relevance 0

Dendritic cells isolated from MHV68 infected mice express IL-10 transcripts, and dendritic cells infected ex vivo secrete IL-10 only when concurrently stimulated with LPS [36].

Localization (secrete) of IL-10 in dendritic cells

2) Confidence 0.79 Published 2008 Journal PLoS Pathogens Section Body Doc Link PMC2270344 Disease Relevance 0.07 Pain Relevance 0.06

Cells transduced with pBluescriptIISK were stimulated with 100 ng/mL of LPS following nucleofection as indicated. 48 hours post-nucleofection, supernatants were harvested and secreted IL-10 measured by ELISA (BD Biosciences).

Localization (secreted) of IL-10

3) Confidence 0.79 Published 2008 Journal PLoS Pathogens Section Body Doc Link PMC2270344 Disease Relevance 0.08 Pain Relevance 0.13

In primary murine B cells, M2-driven proliferation was dependent on the B cell's ability to secrete IL-10 and respond to IL-10 signaling.

Localization (secrete) of IL-10 in B cell

4) Confidence 0.79 Published 2008 Journal PLoS Pathogens Section Body Doc Link PMC2270344 Disease Relevance 0.13 Pain Relevance 0

It has been shown that ex vivo stimulation of MHV68 latently infected splenocytes with MHV68-infected antigen presenting cells resulted in IL-10 secretion peaking at the onset of splenic latency, and B cells were shown to be responsible for a significant portion of the IL-10 secreted [47].

Localization (secreted) of IL-10 in B cells

5) Confidence 0.79 Published 2008 Journal PLoS Pathogens Section Body Doc Link PMC2270344 Disease Relevance 0.06 Pain Relevance 0.07

M2 protein expression leads to secretion of IL-10

Localization (secretion) of IL-10

6) Confidence 0.79 Published 2008 Journal PLoS Pathogens Section Body Doc Link PMC2270344 Disease Relevance 0 Pain Relevance 0.12

Untreated A20 cells secrete significant levels of IL-10, which were only modestly enhanced by LPS treatment (Figure 4F).

Localization (secrete) of IL-10 in A20

7) Confidence 0.79 Published 2008 Journal PLoS Pathogens Section Body Doc Link PMC2270344 Disease Relevance 0.05 Pain Relevance 0.08

These results provide strong evidence that M2 induction of IL-10 secretion, either from latently infected B cells or some other latency reservoir (e.g., infected macrophages or dendritic cells), contributes significantly to the serum levels of IL-10 observed during MHV68 infection following either intranasal or intraperitoneal virus inoculation.

Localization (secretion) of IL-10 in B cells associated with infection

8) Confidence 0.79 Published 2008 Journal PLoS Pathogens Section Body Doc Link PMC2270344 Disease Relevance 0.25 Pain Relevance 0.03

Finally, to further assess the ability of M2 expression to up-regulate IL-10 secretion from B cells, we transfected the murine A20 B cell line with either a control expression vector (pIRES-EGFP) or an M2 expression vector (pM2-IEGFP) and assessed IL-10 secretion by ELISA (Figure 4F).

Localization (secretion) of IL-10 in A20

9) Confidence 0.79 Published 2008 Journal PLoS Pathogens Section Body Doc Link PMC2270344 Disease Relevance 0 Pain Relevance 0.09

It has been shown that ex vivo stimulation of MHV68 latently infected splenocytes with MHV68-infected antigen presenting cells resulted in IL-10 secretion peaking at the onset of splenic latency, and B cells were shown to be responsible for a significant portion of the IL-10 secreted [47].

Localization (secretion) of IL-10 in B cells

10) Confidence 0.79 Published 2008 Journal PLoS Pathogens Section Body Doc Link PMC2270344 Disease Relevance 0.11 Pain Relevance 0.07

Thus, we hypothesize that during M2-mediated reactivation there is concurrent IL-10 secretion, locally dampening the ability of the MHV68-specific CD8+ T cells to clear the infected cells, leading to enhanced establishment and reactivation from latency.

Localization (secretion) of IL-10 in T cells

11) Confidence 0.79 Published 2008 Journal PLoS Pathogens Section Body Doc Link PMC2270344 Disease Relevance 0.29 Pain Relevance 0

These data demonstrate that M2 expression in primary murine B cells leads to enhanced secretion of several cytokines, most notably IL-10.

Localization (secretion) of IL-10 in B cells associated with cytokine

12) Confidence 0.79 Published 2008 Journal PLoS Pathogens Section Body Doc Link PMC2270344 Disease Relevance 0 Pain Relevance 0.10

Finally, to further assess the ability of M2 expression to up-regulate IL-10 secretion from B cells, we transfected the murine A20 B cell line with either a control expression vector (pIRES-EGFP) or an M2 expression vector (pM2-IEGFP) and assessed IL-10 secretion by ELISA (Figure 4F).

Localization (secretion) of IL-10 in A20

13) Confidence 0.79 Published 2008 Journal PLoS Pathogens Section Body Doc Link PMC2270344 Disease Relevance 0 Pain Relevance 0.09

In addition, transfection of the control expression vector had no impact of the levels of IL-10 secreted by A20 cells (Figure 4F).

Neg (no) Localization (secreted) of IL-10 in A20

14) Confidence 0.79 Published 2008 Journal PLoS Pathogens Section Body Doc Link PMC2270344 Disease Relevance 0.07 Pain Relevance 0.08

Interestingly, these investigators showed that M2 is transcribed by infected dendritic cells, although they did not demonstrate that IL-10 secretion was mediated by M2 [36].

Localization (secretion) of IL-10 in dendritic cells

15) Confidence 0.79 Published 2008 Journal PLoS Pathogens Section Body Doc Link PMC2270344 Disease Relevance 0.14 Pain Relevance 0.03

VMD2-IL10 transgenic mice expressed high levels of secreted IL-10 in the retina, and were prone to develop CNV following laser-injury [3].

Localization (secreted) of IL-10 in retina associated with targeted disruption, injury and age-related macular degeneration

16) Confidence 0.75 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2743195 Disease Relevance 1.75 Pain Relevance 0.08

This is in agreement with our findings, as one can expect that released IL-10 in wildtype mice is inactivated by MMP-8.

Localization (released) of IL-10

17) Confidence 0.74 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2951918 Disease Relevance 0.64 Pain Relevance 0.20

SYBR Green detection (Power SYBR® Green PCR Master Mix, Applied Biosystems, Warrington, UK), was used for Il1rn, Il1b, Il10, and Tnf.

Localization (used) of Il10

18) Confidence 0.71 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2765728 Disease Relevance 0.08 Pain Relevance 0.17

This indicates that intact peritoneal macrophages of SWISS mice are important for limiting PMN accumulation, perhaps mainly through the release of IL-10, but are not critical for the induction of anti-inflammatory effects of morphine during the early stages of peritonitis.

Localization (release) of IL-10 in peritoneal macrophages associated with inflammation, peritonitis and morphine

19) Confidence 0.71 Published 2004 Journal Folia Biol. (Krakow) Section Abstract Doc Link 19058564 Disease Relevance 0.49 Pain Relevance 0.44

mice, albeit at lower levels (Figure 8 B), suggesting that cells other than CD4+ T cells (such as macrophages) play a certain but subdominant role in secreting IL-10 during WNV infection in vivo.

Localization (secreting) of IL-10 in macrophages associated with infection

20) Confidence 0.70 Published 2009 Journal PLoS Pathogens Section Body Doc Link PMC2749443 Disease Relevance 0.80 Pain Relevance 0

General Comments

This test has worked.