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PMID: 17276732
TLRs recognize various conserved pathogen-associated molecules, including triacylated lipoproteins (TLR2–TLR1), diacylated lipoproteins (TLR2–TLR6), double-stranded (ds)RNA (TLR3), lipopolysaccharide (LPS) (TLR4), flagellin (TLR5), single-stranded (ss)RNA (TLR8) and unmethylated DNA (TLR9).</csml:comment>
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PMID: 17276732
TLRs recognize various conserved pathogen-associated molecules, including triacylated lipoproteins (TLR2–TLR1), diacylated lipoproteins (TLR2–TLR6), double-stranded (ds)RNA (TLR3), lipopolysaccharide (LPS) (TLR4), flagellin (TLR5), single-stranded (ss)RNA (TLR8) and unmethylated DNA (TLR9).</csml:comment>
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<csml:comments>
<csml:comment type="text">


PMID: 17276732
TLRs recognize various conserved pathogen-associated molecules, including triacylated lipoproteins (TLR2–TLR1), diacylated lipoproteins (TLR2–TLR6), double-stranded (ds)RNA (TLR3), lipopolysaccharide (LPS) (TLR4), flagellin (TLR5), single-stranded (ss)RNA (TLR8) and unmethylated DNA (TLR9).</csml:comment>
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<csml:comment type="text">


PMID: 17276732
TLRs recognize various conserved pathogen-associated molecules, including triacylated lipoproteins (TLR2–TLR1), diacylated lipoproteins (TLR2–TLR6), double-stranded (ds)RNA (TLR3), lipopolysaccharide (LPS) (TLR4), flagellin (TLR5), single-stranded (ss)RNA (TLR8) and unmethylated DNA (TLR9).</csml:comment>
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<csml:comment type="text">


PMID: 17276732
TLRs recognize various conserved pathogen-associated molecules, including triacylated lipoproteins (TLR2–TLR1), diacylated lipoproteins (TLR2–TLR6), double-stranded (ds)RNA (TLR3), lipopolysaccharide (LPS) (TLR4), flagellin (TLR5), single-stranded (ss)RNA (TLR8) and unmethylated DNA (TLR9).</csml:comment>
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<csml:comment type="text">


PMID: 17276732
TLRs recognize various conserved pathogen-associated molecules, including triacylated lipoproteins (TLR2–TLR1), diacylated lipoproteins (TLR2–TLR6), double-stranded (ds)RNA (TLR3), lipopolysaccharide (LPS) (TLR4), flagellin (TLR5), single-stranded (ss)RNA (TLR8) and unmethylated DNA (TLR9).</csml:comment>
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PMID: 17276732, 15001781, 15860593
Murine TLR11 recognizes a protozoan profilin-like protein and uropathogenic bacteria.</csml:comment>
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PMID: 17276732, 15728506
MyD88 directly associates with TLR5, TLR7 and TLR9 and indirectly with TLR2 and TLR4 through another adaptor called MyD88 adaptor-like (MAL) [also known as TIR domain-containing adaptor protein (TIRAP)].</csml:comment>
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PMID: 17276732, 15728506
MyD88 directly associates with TLR5, TLR7 and TLR9 and indirectly with TLR2 and TLR4 through another adaptor called MyD88 adaptor-like (MAL) [also known as TIR domain-containing adaptor protein (TIRAP)].</csml:comment>
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PMID: 17276732, 15728506
MyD88 directly associates with TLR5, TLR7 and TLR9 and indirectly with TLR2 and TLR4 through another adaptor called MyD88 adaptor-like (MAL) [also known as TIR domain-containing adaptor protein (TIRAP)].</csml:comment>
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PMID: 17276732, 11812998
The imidazoquinolines, which currently include imiquimod and resisquimod, are routinely used to treat genital warts and genital herpes, which are caused by the human papilloma virus (HPV) and HSV, respectively. Imiquimod stimulates cells via TLR7 and resisquimod via both TLR7 and TLR8.</csml:comment>
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PMID: 17276732, 15728506
MyD88 directly associates with TLR5, TLR7 and TLR9 and indirectly with TLR2 and TLR4 through another adaptor called MyD88 adaptor-like (MAL) [also known as TIR domain-containing adaptor protein (TIRAP)].</csml:comment>
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PMID: 17276732, 15728506
MyD88 directly associates with TLR5, TLR7 and TLR9 and indirectly with TLR2 and TLR4 through another adaptor called MyD88 adaptor-like (MAL) [also known as TIR domain-containing adaptor protein (TIRAP)].</csml:comment>
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<csml:comment type="text">


PMID: 17276732, 15728506
MyD88 directly associates with TLR5, TLR7 and TLR9 and indirectly with TLR2 and TLR4 through another adaptor called MyD88 adaptor-like (MAL) [also known as TIR domain-containing adaptor protein (TIRAP)].</csml:comment>
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<csml:comment type="text">


PMID: 17276732, 15728506
MyD88 directly associates with TLR5, TLR7 and TLR9 and indirectly with TLR2 and TLR4 through another adaptor called MyD88 adaptor-like (MAL) [also known as TIR domain-containing adaptor protein (TIRAP)].</csml:comment>
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PMID: 17276732
TLRs recognize various conserved pathogen-associated molecules, including triacylated lipoproteins (TLR2–TLR1), diacylated lipoproteins (TLR2–TLR6), double-stranded (ds)RNA (TLR3), lipopolysaccharide (LPS) (TLR4), flagellin (TLR5), single-stranded (ss)RNA (TLR8) and unmethylated DNA (TLR9).</csml:comment>
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PMID: 17276732, 15728506
MyD88 directly associates with TLR5, TLR7 and TLR9 and indirectly with TLR2 and TLR4 through another adaptor called MyD88 adaptor-like (MAL) [also known as TIR domain-containing adaptor protein (TIRAP)].</csml:comment>
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PMID: 17276732, 11812998
The imidazoquinolines, which currently include imiquimod and resisquimod, are routinely used to treat genital warts and genital herpes, which are caused by the human papilloma virus (HPV) and HSV, respectively. Imiquimod stimulates cells via TLR7 and resisquimod via both TLR7 and TLR8.</csml:comment>
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PMID: 17276732, 16675322
Similar to MyD88–TIRAP complex, TRIF associates directly with TLR3 and indirectly with TLR4 through TRIF-related adaptor molecule (TRAM).</csml:comment>
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PMID: 17276732, 16675322
Similar to MyD88–TIRAP complex, TRIF associates directly with TLR3 and indirectly with TLR4 through TRIF-related adaptor molecule (TRAM).</csml:comment>
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<csml:comment type="text">
</csml:comment>
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<csml:parameter key="coefficient1" value="0.1"/>
<csml:parameter key="coefficient2" value="1.0"/>
</csml:processKinetic>
</csml:processSimulationProperty>
<csml:viewProperty>
<csml:position position="auto" positionID="default" x="1031.0" y="483.0"/>
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PMID: 17276732, 16675322
Similar to MyD88–TIRAP complex, TRIF associates directly with TLR3 and indirectly with TLR4 through TRIF-related adaptor molecule (TRAM).</csml:comment>
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</csml:process>
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<csml:comment type="text">

PMID: 17276732
Interestingly, activation of TLR7, TLR8 and TLR9 results in MyD88-dependent production of IFN-alpha, in contrast to the TLR3- and TLR4-mediated IFN-beta production, which is MyD88-independent.</csml:comment>
</csml:comments>
</csml:process>
<csml:process id="p23" name="p23" type="cso30:c:ProcessBiological">
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</csml:comment>
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</csml:comment>
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<csml:comment type="text">
</csml:comment>
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<csml:comment type="text">

PMID: 17276732
Interestingly, activation of TLR7, TLR8 and TLR9 results in MyD88-dependent production of IFN-alpha, in contrast to the TLR3- and TLR4-mediated IFN-beta production, which is MyD88-independent.</csml:comment>
</csml:comments>
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Indirect</csml:comment>
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Indirect</csml:comment>
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</csml:comment>
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<csml:comment type="text">

PMID: 17276732
Interestingly, activation of TLR7, TLR8 and TLR9 results in MyD88-dependent production of IFN-alpha, in contrast to the TLR3- and TLR4-mediated IFN-beta production, which is MyD88-independent.</csml:comment>
</csml:comments>
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<csml:comment type="text">
Indirect</csml:comment>
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Indirect</csml:comment>
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PMID: 17276732
Interestingly, activation of TLR7, TLR8 and TLR9 results in MyD88-dependent production of IFN-alpha, in contrast to the TLR3- and TLR4-mediated IFN-beta production, which is MyD88-independent.</csml:comment>
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PMID: 17276732
Interestingly, activation of TLR7, TLR8 and TLR9 results in MyD88-dependent production of IFN-alpha, in contrast to the TLR3- and TLR4-mediated IFN-beta production, which is MyD88-independent.</csml:comment>
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PMID: 17276732
Interestingly, activation of TLR7, TLR8 and TLR9 results in MyD88-dependent production of IFN-alpha, in contrast to the TLR3- and TLR4-mediated IFN-beta production, which is MyD88-independent.</csml:comment>
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PMID: 17276732
Interestingly, activation of TLR7, TLR8 and TLR9 results in MyD88-dependent production of IFN-alpha, in contrast to the TLR3- and TLR4-mediated IFN-beta production, which is MyD88-independent.</csml:comment>
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PMID: 17276732
Interestingly, activation of TLR7, TLR8 and TLR9 results in MyD88-dependent production of IFN-alpha, in contrast to the TLR3- and TLR4-mediated IFN-beta production, which is MyD88-independent.</csml:comment>
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PMID: 17276732
Studies have shown that TLR7 and TLR9 stimulation results in the activation of IRF-7, whereas IRF-5 is activated by TLR7 and TLR8.</csml:comment>
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PMID: 17276732
Studies have shown that TLR7 and TLR9 stimulation results in the activation of IRF-7, whereas IRF-5 is activated by TLR7 and TLR8.</csml:comment>
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PMID: 17276732
Studies have shown that TLR7 and TLR9 stimulation results in the activation of IRF-7, whereas IRF-5 is activated by TLR7 and TLR8.</csml:comment>
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PMID: 17276732
Studies have shown that TLR7 and TLR9 stimulation results in the activation of IRF-7, whereas IRF-5 is activated by TLR7 and TLR8.</csml:comment>
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PMID: 17276732
Studies have shown that TLR7 and TLR9 stimulation results in the activation of IRF-7, whereas IRF-5 is activated by TLR7 and TLR8.</csml:comment>
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PMID: 17276732
The MyD88-dependent signaling pathway induces translocation of the transcription factor nuclear factor-kappaB (NF-kappaB) into the nucleus, resulting in the transcription of immune genes.</csml:comment>
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PMID: 17276732
The outcomes of the NF-kappaB-mediated transcription include the production and secretion of inflammatory cytokines, and the induction of direct antimicrobial mechanisms.</csml:comment>
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PMID: 17276732
By contrast, the TRIF-mediated pathway, which is commonly known as the MyD88-independent pathway, results in the activation of interferon regulatory factor-3 (IRF-3), leading to the transcription of type 1 interferons (IFNs).</csml:comment>
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PMID: 17276732
By contrast, the TRIF-mediated pathway, which is commonly known as the MyD88-independent pathway, results in the activation of interferon regulatory factor-3 (IRF-3), leading to the transcription of type 1 interferons (IFNs).</csml:comment>
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PMID: 17276732
By contrast, the TRIF-mediated pathway, which is commonly known as the MyD88-independent pathway, results in the activation of interferon regulatory factor-3 (IRF-3), leading to the transcription of type 1 interferons (IFNs).</csml:comment>
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PMID: 17276732
Although it is clear that TLR activation results in the expression of antimicrobial peptides, especially human defensin beta4 (DEFB4), little is known about the TLR-induced direct antimicrobial functions in epithelial cells.</csml:comment>
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PMID: 17276732
Although it is clear that TLR activation results in the expression of antimicrobial peptides, especially human defensin beta4 (DEFB4), little is known about the TLR-induced direct antimicrobial functions in epithelial cells.</csml:comment>
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PMID: 17276732, 12411706
DEFB4 can also induce dendritic-cell activation and maturation in a TLR4-dependent manner.</csml:comment>
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PMID: 17276732, 12411706
DEFB4 can also induce dendritic-cell activation and maturation in a TLR4-dependent manner.</csml:comment>
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PMID: 17276732, 10426995
In 1999, it was demonstrated that activation of TLR2 by its ligand, the Mycobacterium tuberculosis-derived 19-kDa lipoprotein, resulted in the activation of host-defense mechanisms from monocytes and macrophages, including the secretion of cytokines and inducible nitric-oxide synthase (iNOS) promoter activity.

PMID: 17276732
This was shown by using iNOS inhibitors l-NIL and l-NAME, which could ablate the TLR2-mediated antimicrobial activity in murine cells, but had no effect on human cells.</csml:comment>
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PMID: 17276732, 10426995
In 1999, it was demonstrated that activation of TLR2 by its ligand, the Mycobacterium tuberculosis-derived 19-kDa lipoprotein, resulted in the activation of host-defense mechanisms from monocytes and macrophages, including the secretion of cytokines and inducible nitric-oxide synthase (iNOS) promoter activity.</csml:comment>
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PMID: 17276732, 10426995
In 1999, it was demonstrated that activation of TLR2 by its ligand, the Mycobacterium tuberculosis-derived 19-kDa lipoprotein, resulted in the activation of host-defense mechanisms from monocytes and macrophages, including the secretion of cytokines and inducible nitric-oxide synthase (iNOS) promoter activity.

PMID: 17276732
This was shown by using iNOS inhibitors l-NIL and l-NAME, which could ablate the TLR2-mediated antimicrobial activity in murine cells, but had no effect on human cells.</csml:comment>
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PMID: 17276732, 10426995
In 1999, it was demonstrated that activation of TLR2 by its ligand, the Mycobacterium tuberculosis-derived 19-kDa lipoprotein, resulted in the activation of host-defense mechanisms from monocytes and macrophages, including the secretion of cytokines and inducible nitric-oxide synthase (iNOS) promoter activity.</csml:comment>
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PMID: 17276732, 12960280
Although most mammals have multiple cathelicidin family members, humans have only one type of cathelicidin, which is encoded by the hCAP18 gene.</csml:comment>
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PMID; 17276732, 11389039
Human cathelicidin is stored as a 17-kDa pre-propeptide or cationic antimicrobial peptide (hCAP-18) in secretory granules, and is then processed into a mature 5-kDa form (LL-37) by protease-3 during or after secretion.</csml:comment>
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PMID: 17276732, 16083775
In addition, some of the DEFB members function as chemoattractants for neutrophils, immature dendritic cells and memory T cells through interaction with chemokine (C-C motif) receptor 6 (CCR-6).</csml:comment>
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PMID: 17276732, 16497887
However, it was recently demonstrated that TLR activation in human monocytes results in the expression of the vitamin-D receptor (VDR) and the 1alpha-vitamin D hydroxylase (Cyp27B1).</csml:comment>
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PMID: 17276732, 16497887
However, it was recently demonstrated that TLR activation in human monocytes results in the expression of the vitamin-D receptor (VDR) and the 1alpha-vitamin D hydroxylase (Cyp27B1).</csml:comment>
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PMID: 17276732
The gene product of Cyp27B1 converts inactive vitamin D3 prohormone (25D3) into its active form (1,25D3), which can then bind to and activate the VDR.</csml:comment>
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PMID: 17276732
The gene product of Cyp27B1 converts inactive vitamin D3 prohormone (25D3) into its active form (1,25D3), which can then bind to and activate the VDR.</csml:comment>
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PMID: 17276732
Activation of the VDR in monocytes results in the expression of the antimicrobial peptide cathelicidin in its active LL-37 form.</csml:comment>
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PMID: 17276732
The gene product of Cyp27B1 converts inactive vitamin D3 prohormone (25D3) into its active form (1,25D3), which can then bind to and activate the VDR.</csml:comment>
</csml:comments>
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PMID: 17276732
Interestingly, the ability of TLR2–TLR1 activation to induce cathelicidin mRNA expression depends on adequate 25D3 concentrations in the serum that is used to culture the cells.</csml:comment>
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PMID: 17276732, 9632843, 14749681
There is evidence that iNOS gene expression is regulated by the VDR in both species.</csml:comment>
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PMID: 17276732, 16040207, 14550285
Furthermore, VDR activation was demonstrated to downregulate transcription of Trp–Asp-containing coat protein (TACO) [45], which has a role in M. tuberculosis entry and survival in human macrophages.</csml:comment>
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PMID: 17276732, 15728506, 15634923
Stimulation of UECs with dsRNA upregulates mRNA expression of antiviral genes IFN-beta, myxovirus resistance gene [1] and 2′,5′ olioadenylate.</csml:comment>
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PMID: 17276732, 16982913
Also in 2006, it was demonstrated that TLR3 activation on human fetal astrocytes results in an antiviral state that arises from the TLR3-dependent induction of viperin (also known as cig5) against a pseudotyped HIV particle.</csml:comment>
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PMID: 17276732, 15728506, 15634923
Stimulation of UECs with dsRNA upregulates mRNA expression of antiviral genes IFN-beta, myxovirus resistance gene [1] and 2′,5′ olioadenylate.</csml:comment>
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PMID: 17276732
In 2001, the 1,25D3-induced antimicrobial activity was reported to be regulated by phosphatidylinositol 3-kinase (PI3-K) and mediated by the generation of oxygen intermediates via nicotinamide adenine dinucleotide phosphate (NADPH)-dependent phagocyte oxidase.</csml:comment>
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PMID: 17276732, 16116638
Another TLR7 agonist, isatoribine, is effective against hepatitis C.</csml:comment>
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PMID: 17276732, 16763660
However, a class of TLR9-stimulating CpG oligonucleotides is currently undergoing human clinical trials for the treatment of hepatitis B [54] and, if successful, it can yield a new class of antiviral therapeutic compounds.</csml:comment>
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PMID: 17276732, 16497887, 16402404
Both vitamin D3 and vitamin A derivatives, such as 1alpha,25-dihydroxyvitamin D3 and all-trans retinoic acid, decrease cell surface expression of TLRs and dampen their function.</csml:comment>
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<csml:comment type="text">PMID: 17276732
The intracellular pool of 25D3 is shuttled into the cell via the vitamin D binding protein (DBP).</csml:comment>
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<csml:comment type="text">PMID: 17276732
The intracellular pool of 25D3 is shuttled into the cell via the vitamin D binding protein (DBP).</csml:comment>
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