CYP11A1-derived vitamin D3 products protect against UVB-induced inflammation and promote keratinocytes differentiation
Authors: Tae-Kang Kim
Zorica Janjetovic
Uraiwan Panich
Robert C Tuckey
Chander Raman
Wei Li
Anyamanee Chaiprasongsuk
Andrzej T Slominski
Journal: Free Radical Biology and Medicine (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Epidermal structure; Keratinocyte differentiation; Photobiology; UV Radiation.
Affiliations: Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL, USA; Faculty of Medicine and Public Health, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand; Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand., Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL, USA., School of Molecular Sciences, The University of Western Australia, Perth, WA, Australia., Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN, USA., Department of Medicine and Microbiology, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA., Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand., Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL, USA; VA Medical Center, Birmingham, AL, USA. Electronic address: .

Abstract:  UVB radiation mediates inflammatory responses causing skin damage and defects in epidermal differentiation. 1α,25-Dihydroxyvitamin D3 (1,25(OH)2D3) interacts with the vitamin D3 receptor (VDR) to regulate inflammatory responses. Additionally, 1,25(OH)2D3/VDR signaling represents a potential therapeutic target in the treatment of skin disorders associated with inflammation and poor differentiation of keratinocytes. Since the protective effect of 1,25(OH)2D3 against UVB-induced skin damage and inflammation is recognized, CYP11A1-derived vitamin D3-hydroxyderivatives including 20(OH)D3, 1,20(OH)2D3, 20,23(OH)2D3 and 1,20,23(OH)3D3 were tested for their anti-inflammatory and skin protection properties in UVB-irradiated human epidermal keratinocytes (HEKn). HEKn were treated with secosteroids for 24 h pre- and post-UVB (50 mJ/cm2) irradiation. Secosteroids modulated the expression of the inflammatory response genes (IL-17, NF-κB p65, and IκB-α), reducing nuclear-NF-κB-p65 activity and increasing cytosolic-IκB-α expression as well as that of pro-inflammatory mediators, IL-17, TNF-α, and IFN-γ. They stimulated the expression of involucrin (IVL) and cytokeratin 10 (CK10), the major markers of epidermal differentiation, in UVB-irradiated cells. We conclude that CYP11A1-derived hydroxyderivatives inhibit UVB-induced epidermal inflammatory responses through activation of IκB-α expression and suppression of NF-kB-p65 activity and its downstream signaling cytokines, TNF-α, and IFN-γ, as well as by inhibiting IL-17 production and activating epidermal differentiation. 

Retracted: No

PubPeer comments:
 Splice seems to be evident in upper image of Figure 1c but not in the lower. Could the authors please post the original uncropped scan? *** Inverse, contrast enhanced ![file] *** Original ![file] , 
 Figure 6c has an unexpected repeated pattern in the noise, illustrated with the red boxes. Can the authors explain? Perhaps the uncropped scans could address this. *** Original ![file] *** False color ![file] , 
 I believe that these are in the Western blot supplemental documents. We can upload the files here. Please instruct how to do this , 
 Thank you for your reply. You may post those here (link below) or use a link to an external site (such as Imgur.com) for larger files. I was unable to retrieve these from the journal site. You may also be interested in reviewing this other thread which appears to predate the first authoru2019s affiliation with your team: https: pubpeer.com publications A4DBD18A818675ECFDAD563BB622FF I am continuing my review of related papers. *** ![file] , 
 Thank you. I have the files in power point (two), but I believe they have to be changed into jpg. Are two separate jpg appropriate? Thank you again for allowing to deposit the uncropped blots. , 
 #5 Thank you for your efforts. Two image files should be fine. If you wish to share the original .ppt files, you can do so by storing them on Google Drive or Dropbox and posting a link here. , 
 ![file] ![file] The uncropped files are attached , 
 #7 Thank you for sending. May I ask which author prepared the uncropped files in this reply? , 
 First author and it was reviewed by Dr Janjetovic who supervised her in the past and by me and we discussed. Anya has a good position in Thailand, she was extremely precise during her training in my lab. Everybody was impressed with her attention to detail , 
 #9 Thank you for responding. The u201coriginalu201d provided appears to have been edited to remove *only* the repetitive pattern indicated with the red boxes in #2. The background noise elsewhere appears identical; I have juxtaposed those images (both in false color) below. I am unable to understand how this could occur by chance. Could the authors explain? High resolution: https: imgur.com gallery 9d7tazJ ![file] , 
 We used autoradiography, x-ray film and exposure plus development. Yes this was very traditional but very solid. Also since blots were reproved they were covered with sraraps, I believe to keep them wet. We have holidays, if you have additional questions I will check on Tuesday ,