7/26/2019 Journal Review: Intestinal Alkaline Phosphatase Detoxifies Lipopolysaccharide and Prevents Inflammation in Zebrafish in Response to the Gut Microbiota

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Intestinal AlkalinePhosphatase Detoxifes

Lipopolysaccharide andPrevents Inammation in

Zebrafsh in Response to t

Gut icrobiota!enni"er # $ates% !anie Akerlund% &rika itt'e% and (

Guillemin

Cell Host & Microbe)* +,-.+/)% )00,

7/26/2019 Journal Review: Intestinal Alkaline Phosphatase Detoxifies Lipopolysaccharide and Prevents Inflammation in Zebrafish in Response to the Gut Microbiota

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Introduction

LP1

a2orconstituent o"

outer membraneo" Gram.ne'ativebacteria

&ndotoxin

3verstimulatin' 4LRsi'nalin'5 yD// as

adaptor "ortranscription o"

proinammatorycytokines% e#'# 467

Inducinpermea

o8% recruitm

shocdys"un

Rmso

Inappropriateinammatory

response

odifcation o"proinammatory

microbialmolecule

Alkalinephosphatase

9AP:dephosphorylate

s lipid A o" LP1

7/26/2019 Journal Review: Intestinal Alkaline Phosphatase Detoxifies Lipopolysaccharide and Prevents Inflammation in Zebrafish in Response to the Gut Microbiota

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Introduction

Zebrafsh

$acterial association and'ene expression can be

manipulatedrespectively usin'

'notobiolo'y andmorpholino antisenseoli'onucleotides 93s:

Developphysiolo'y

and ma

di'estive trsim

7/26/2019 Journal Review: Intestinal Alkaline Phosphatase Detoxifies Lipopolysaccharide and Prevents Inflammation in Zebrafish in Response to the Gut Microbiota

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;ypothesis

Intestinal alkaline phosphatase 9Iap: dephosphoryLP1 associated 8ith 'ut bacteria% thereby modulaintestinal inammation in response to the residenmicrobiota#

7/26/2019 Journal Review: Intestinal Alkaline Phosphatase Detoxifies Lipopolysaccharide and Prevents Inflammation in Zebrafish in Response to the Gut Microbiota

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&xperimental Procedures

Iap Activity andiap4ranscript Levels

uantitative R4

determine expression p'ene

Incubatin' tissue homop.nitrophenylphospabsorbance measur

>uanti"y AP act

?uantitative Real.4ime Puanti"y iap transcript level

7/26/2019 Journal Review: Intestinal Alkaline Phosphatase Detoxifies Lipopolysaccharide and Prevents Inflammation in Zebrafish in Response to the Gut Microbiota

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&xperimental Procedures4oxicity o" LP1

&xposure o" LP1 9+0% @0% -@0% )@0'BmL: to 8ild.type =ebrafsh

1urvival rate and ;Chistolo'y o" liver to det

eect o" LP1

&xposure o" @0 'BmL LP1 to 8ild.type and myd88.3.in2ected

=ebrafsh5 exposure o" @0 'BmLuanti"y tnfa and tnfb

level

&xposure o" LP1 9+0% @0% -@0% )@0'BmL: to 8ild.type =ebrafsh

yeloid peroxidase 9histolo'y o" esopha'e

2unction 9ei2: and liver ttoxic eect o"

&xposure o" LP1 9-@0 or )@0 'BmL:to myd88.3.in2ected and tnfr1.3.

in2ected =ebrafsh

1urvival rat

7/26/2019 Journal Review: Intestinal Alkaline Phosphatase Detoxifies Lipopolysaccharide and Prevents Inflammation in Zebrafish in Response to the Gut Microbiota

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&xperimental Procedures

Detoxifcation o" LP1 ?uantifcation o" survived larvae

7/26/2019 Journal Review: Intestinal Alkaline Phosphatase Detoxifies Lipopolysaccharide and Prevents Inflammation in Zebrafish in Response to the Gut Microbiota

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&xperimental Procedures

Intestinal 6eutrophil Infltration ?uantifcation o" number o" neutrophil in 8hole

and transverse section o" distal part o" =ebrafshstained 8ith po

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Results

Iap Activity andiap4ranscript Levels

7/26/2019 Journal Review: Intestinal Alkaline Phosphatase Detoxifies Lipopolysaccharide and Prevents Inflammation in Zebrafish in Response to the Gut Microbiota

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ResultsLP1 4oxicity

7/26/2019 Journal Review: Intestinal Alkaline Phosphatase Detoxifies Lipopolysaccharide and Prevents Inflammation in Zebrafish in Response to the Gut Microbiota

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Results

Detoxifcation o" LP1

7/26/2019 Journal Review: Intestinal Alkaline Phosphatase Detoxifies Lipopolysaccharide and Prevents Inflammation in Zebrafish in Response to the Gut Microbiota

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ResultsIntestinal 6eutrophil Infltration

7/26/2019 Journal Review: Intestinal Alkaline Phosphatase Detoxifies Lipopolysaccharide and Prevents Inflammation in Zebrafish in Response to the Gut Microbiota

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ResultsIntestinal 6eutrophil Infltration

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Discussion

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