Caffeoyl-Prolyl-Histidine Amide Inhibits Fyn and Alleviates Atopic Dermatitis-Like Phenotypes via Suppression of NF-κB Activation
, Dong-Sik Shin 2, Sunhyae Jang 3,4,5, Kyu Han Kim 3,4,5, Seok-In Kim 6, Yoon-Sik Lee 6 and Bong-Gun Ju 1,*Round 1
Reviewer 1 Report
This is an interesting article regarding the caffeic acid (CA) and caffeoyl-prolyl-histidine amide. CA is conjugated with proline-histidine dipeptide, relieves atopic dermatitis (AD)- like phenotypes in mouse. The authors investigated the molecular mechanism underlying CA- PH-mediated alleviation of AD-like phenotypes using cell line and AD mouse model and they confirmed that CA-PH suppresses AD-like phenotypes such as increased epidermal thickening, infiltration of mast cells, and dysregulated gene expression of cytokines. CA-PH suppressed up-regulation of cytokine expression through inhibition of nuclear translocation of NF-κB. Using a CA-PH affinity pull-down assay, they found that CA-PH binds to Fyn. In silico molecular docking and enzyme kinetic studies revealed that CA-PH binds to the ATP binding site and inhibits Fyn competitively with ATP.
The authors suggest that CA-PH treatment may help to reduce skin inflammation via down-regulation of NF-κB activation, and Fyn may be a new therapeutic target of skin inflammatory diseases such as AD.
Author Response
We appreciate the Reviewer1 for the positive comments.
Reviewer 2 Report
The manuscript of Jeong et al aims to elucidate the molecular mechanism underlying the therapeutic action of caffeoyl-prolyl-histidine amide. The manuscript uses kinetic, pharmacologic and molecular methods in their investigation that are more than adequate for their conclusions. The article is of important, novel and describes a new (future) treatment option for atopic dermatitis. One minor comment to the authors that will help the readers: the method section should be clear and detailed, and allow method duplication by others. For instance: Antibodies dilutions, incubation times, dehydration time and gradient, dual-luciferase reporter assay [ transfection, plasmid design…ext ] , rna amount in PCR…and so on
Author Response
We appreciate the Reviewer 2 for the valuable comments. We double checked spells and modified Material and Methods as Rivewer2 suggested. We believe that our manuscript is greatly improved.
