Reviewer's report
Title:Activation of the Prostaglandin D2 metabolic pathway in Crohn's disease:
involvement of the enteric nervous system
Version:3Date:21 April 2015
Reviewer: Manolis Roulis
Reviewer's report:
In this manuscript Anne-Gaelle Le Loupp and coworkers examine the activation
of the PGD2 pathway in CD patients with colonic involvement and also
investigate the role of the enteric nervous system as a cellular source of PGD2 in
CD. By analyzing human samples and also employing primary ENS cultures and
neuro-glial co-cultures the authors provide evidence for the following:
1. Gene expression levels of key enzymes for PGD2 synthesis, such as cPLA2,
COX1, COX2 and L-PGDS are increased in the colon of patients with active CD
compared to either matched non-inflamed tissues or tissues from patients with
quiescent CD or tissues from healthy control tissues.
2. PGD2 levels are increased in the inflamed colon of patients with active CD
compared to matched non-inflamed tissues.
3. LPGDS expression is detected in human myenteric and submucosal plexi.
4. LPGDS expression is detected in primary ENS cultures from rats.
5. LPS induces PGD2 secretion by primary primary rat neurons or glial cells
isolated from rats. Treatment with an LPGDS-specific inhibitor abolishes this
induction.
The scientific question addressed in this manuscript is clearly defined, the
experimental procedures well-described and the main conclusions of the study
justified based on the data presented. The authors also discuss their findings
with regard to current relevant literature in the field and the manuscript is clearly
written.
Minor Essential Revisions
1. Figure 4: The origin of the tissues used for LPGDS staining (healthy or CD)
and n= information should be mentioned in the legend. Did the authors compare
healthy vs CD tissues for LPGDS expression by immunostaining? This
comparison would help clarify whether the increased LPGDS gene expression
measured in inflamed CD tissues (Fig.2E) results from the activation of the ENS
or it is sth secondary to the accumulation of inflammatory cells in the tissue.
2. The authors conclude in the abstract that “Our study suggests that the ENS is
involved in CD p a t h o g e n e s i s through PGD2 pathway”. Since the
functional role of PGD2 activation in the inflamed gut (pathogenic or homeostatic)
has not been directly addressed in this study, this conclusion should be
rephrased.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests
Reviewer's report
Title:Activation of the Prostaglandin D2 metabolic pathway in Crohn's disease:
involvement of the enteric nervous system
Version:3Date:21 April 2015
Reviewer: Manolis Roulis
Reviewer's report:
In this manuscript Anne-Gaelle Le Loupp and coworkers examine the activation
of the PGD2 pathway in CD patients with colonic involvement and also
investigate the role of the enteric nervous system as a cellular source of PGD2 in
CD. By analyzing human samples and also employing primary ENS cultures and
neuro-glial co-cultures the authors provide evidence for the following:
1. Gene expression levels of key enzymes for PGD2 synthesis, such as cPLA2,
COX1, COX2 and L-PGDS are increased in the colon of patients with active CD
compared to either matched non-inflamed tissues or tissues from patients with
quiescent CD or tissues from healthy control tissues.
2. PGD2 levels are increased in the inflamed colon of patients with active CD
compared to matched non-inflamed tissues.
3. LPGDS expression is detected in human myenteric and submucosal plexi.
4. LPGDS expression is detected in primary ENS cultures from rats.
5. LPS induces PGD2 secretion by primary primary rat neurons or glial cells
isolated from rats. Treatment with an LPGDS-specific inhibitor abolishes this
induction.
The scientific question addressed in this manuscript is clearly defined, the
experimental procedures well-described and the main conclusions of the study
justified based on the data presented. The authors also discuss their findings
with regard to current relevant literature in the field and the manuscript is clearly
written.
Minor Essential Revisions
1. Figure 4: The origin of the tissues used for LPGDS staining (healthy or CD)
and n= information should be mentioned in the legend. Did the authors compare
healthy vs CD tissues for LPGDS expression by immunostaining? This
comparison would help clarify whether the increased LPGDS gene expression
measured in inflamed CD tissues (Fig.2E) results from the activation of the ENS
or it is sth secondary to the accumulation of inflammatory cells in the tissue.
2. The authors conclude in the abstract that “Our study suggests that the ENS is
involved in CD p a t h o g e n e s i s through PGD2 pathway”. Since the
functional role of PGD2 activation in the inflamed gut (pathogenic or homeostatic)
has not been directly addressed in this study, this conclusion should be
rephrased.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests
Please review this paper.
user
Reviewer's report
Title:Activation of the Prostaglandin D2 metabolic pathway in Crohn's disease:
involvement of the enteric nervous system
Version:3Date:21 April 2015
Reviewer: Manolis Roulis
Reviewer's report:
In this manuscript Anne-Gaelle Le Loupp and coworkers examine the activation
of the PGD2 pathway in CD patients with colonic involvement and also
investigate the role of the enteric nervous system as a cellular source of PGD2 in
CD. By analyzing human samples and also employing primary ENS cultures and
neuro-glial co-cultures the authors provide evidence for the following:
1. Gene expression levels of key enzymes for PGD2 synthesis, such as cPLA2,
COX1, COX2 and L-PGDS are increased in the colon of patients with active CD
compared to either matched non-inflamed tissues or tissues from patients with
quiescent CD or tissues from healthy control tissues.
2. PGD2 levels are increased in the inflamed colon of patients with active CD
compared to matched non-inflamed tissues.
3. LPGDS expression is detected in human myenteric and submucosal plexi.
4. LPGDS expression is detected in primary ENS cultures from rats.
5. LPS induces PGD2 secretion by primary primary rat neurons or glial cells
isolated from rats. Treatment with an LPGDS-specific inhibitor abolishes this
induction.
The scientific question addressed in this manuscript is clearly defined, the
experimental procedures well-described and the main conclusions of the study
justified based on the data presented. The authors also discuss their findings
with regard to current relevant literature in the field and the manuscript is clearly
written.
Minor Essential Revisions
1. Figure 4: The origin of the tissues used for LPGDS staining (healthy or CD)
and n= information should be mentioned in the legend. Did the authors compare
healthy vs CD tissues for LPGDS expression by immunostaining? This
comparison would help clarify whether the increased LPGDS gene expression
measured in inflamed CD tissues (Fig.2E) results from the activation of the ENS
or it is sth secondary to the accumulation of inflammatory cells in the tissue.
2. The authors conclude in the abstract that “Our study suggests that the ENS is
involved in CD p a t h o g e n e s i s through PGD2 pathway”. Since the
functional role of PGD2 activation in the inflamed gut (pathogenic or homeostatic)
has not been directly addressed in this study, this conclusion should be
rephrased.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests
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