Vitamin D and the NLRP3 Inflammasome
Round 1
Reviewer 1 Report
The topic is of interest, however, the paper requires revisions.
Most important the factual inaccuracies have to be corrected, see below.
- Vitamin D is not a hormone, it is a precursor to hormonal hydroxyderivatives. Also better to use the term secosteroid instead of steroid.
- Ergosterol is vitamin D2 but not 25(OH)D2, while cholecaciferol is vitamin D3 but not 25(OH)D3. Both 25(OH)D3 and 25(OH)D3 are generated by hydroxylation in position C25, either locally (D3) or at systemic level (D2 and D3).
- Vitamin D3 is formed through UVB induced conversion of 7-dehydrocholesterol, and it can be further hydroxyklated to 25(OH)D3. 25(OH)D3 is not a product of 7-dehydrocholesterol phototransformation.
- In the text please correct information on vitamin D3 supply in different clinical trials. It is Vitamin D 3 supplied in IU but not 25(OH)D3
Other comments
Use correct abbreviation for hydroxyderivatives of vitamin D, e.,g. 25(OH)D3 or D2 instead of 25(OH)-VD. The same is for 1,25(OH)2D
Mention alternative pathways of vitamin D activation by CYP11A1 (FASEB J 26, 3901–3915, 2012; Mol Cellular Endocrinol 383, 181-192, 2014; Sci. Rep. 5, 14875; doi: 10.1038/srep14875 (2015).
Mention alternative nuclear receptors for active forms of vitamin D including retinoic acid orphan receptors (RORs) (FASEB J 28:2775-2789, 2014; Cell Biochem Biophys 78(2):165-180, 2020) and AhR (In J Mol Sci 2018, 19 (10), 30)
The readers would also appreciate information on photoprotective functions of active forms of vitamin D.
I believe that in figure 1 legend a comment that permission to reuse the figure was obtained from MDPI
The readers would appreciate a figure showing chemical structures of ergosterol, 7-dehydrocholesterol, vitamin D3 and D3.
Author Response
The topic is of interest, however, the paper requires revisions.
Most important the factual inaccuracies have to be corrected, see below.
- Vitamin D is not a hormone, it is a precursor to hormonal hydroxyderivatives. Also better to use the term secosteroid instead of steroid.
Thank you for pointing this out. Please find corrected terminology in the revised manuscript.
- Ergosterol is vitamin D2 but not 25(OH)D2, while cholecaciferol is vitamin D3 but not 25(OH)D3. Both 25(OH)D3 and 25(OH)D3 are generated by hydroxylation in position C25, either locally (D3) or at systemic level (D2 and D3).
Please find changed abbreviations in the draft. We tried to be as accurate and consistent as possible with our abbreviations.
- Vitamin D3 is formed through UVB induced conversion of 7-dehydrocholesterol, and it can be further hydroxyklated to 25(OH)D3. 25(OH)D3 is not a product of 7-dehydrocholesterol phototransformation.
Thank you for your comments. We have amended the manuscript accordingly. Please find this information in Figure 1.
- In the text please correct information on vitamin D3 supply in different clinical trials. It is Vitamin D 3 supplied in IU but not 25(OH)D3
Thank you. Manuscript amended.
Other comments
Use correct abbreviation for hydroxyderivatives of vitamin D, e.,g. 25(OH)D3 or D2 instead of 25(OH)-VD. The same is for 1,25(OH)2D
Manuscript was amended
Mention alternative pathways of vitamin D activation by CYP11A1 (FASEB J 26, 3901–3915, 2012; Mol Cellular Endocrinol 383, 181-192, 2014; Sci. Rep. 5, 14875; doi: 10.1038/srep14875 (2015).
Mention alternative nuclear receptors for active forms of vitamin D including retinoic acid orphan receptors (RORs) (FASEB J 28:2775-2789, 2014; Cell Biochem Biophys 78(2):165-180, 2020) and AhR (In J Mol Sci 2018, 19 (10), 30)
We appreciate the references, which were included alongside additional wording in the revised manuscript.
The readers would also appreciate information on photoprotective functions of active forms of vitamin D.
Manuscript was amended.
I believe that in figure 1 legend a comment that permission to reuse the figure was obtained from MDPI
We obtained permission from the publisher. Requested info was provided in the legend.
The readers would appreciate a figure showing chemical structures of ergosterol, 7-dehydrocholesterol, vitamin D3 and D3.
Please refer to Figure 1.
Reviewer 2 Report
While many different sources are used to set up the study in the introduction, little previous evidence is stated. The introduction is thus short and poorly sets up the rationale for the study. More attention to how this study fits into previous work in NLRP3 and inflammation should be added to improve this section. Please refer to doi: 10.3390/ijms21124223, 10.3390/biology9090238, 10.3390/antiox9100992.
Author Response
While many different sources are used to set up the study in the introduction, little previous evidence is stated. The introduction is thus short and poorly sets up the rationale for the study. More attention to how this study fits into previous work in NLRP3 and inflammation should be added to improve this section. Please refer to doi: 10.3390/ijms21124223, 10.3390/biology9090238, 10.3390/antiox9100992.
Thank you very much for your feedback. We have amended our introduction section and included the suggested references.
