PMID- 35216228 OWN - NLM STAT- MEDLINE DCOM- 20220314 LR - 20220314 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 23 IP - 4 DP - 2022 Feb 14 TI - An Interleukin-4 and Interleukin-13 Induced Atopic Dermatitis Human Skin Equivalent Model by a Skin-On-A-Chip. LID - 10.3390/ijms23042116 [doi] LID - 2116 AB - Currently, the mechanism of progression of atopic dermatitis (AD) is not well understood because there is no physiologically appropriate disease model in terms of disease complexity and multifactoriality. Type 2 inflammation, mediated by interleukin (IL)-4 and IL-13, plays an important role in AD. In this study, full-thickness human skin equivalents consisting of human-derived cells were fabricated from pumpless microfluidic chips and stimulated with IL-4 and IL-13. The morphological properties, gene expression, cytokine secretion and protein expression of the stimulated human skin equivalent (HSE) epidermis were investigated. The results showed epidermal and spongy formations similar to those observed in lesions in AD, and decreased expression of barrier-related filaggrin, loricrin and involucrin genes and proteins induced by IL-4Ralpha signaling. In addition, we induced the expression of carbonic anhydrase II (CAII), a gene specifically expressed in the epidermis of patients with AD. Thus, AD human skin equivalents can be used to mimic the key pathological features of atopic dermatitis, overcoming the limitations of existing studies that rely solely on mouse models and have been unable to translate their effects to humans. Our results will be useful for future research on the development of therapeutic agents for atopic dermatitis. FAU - Kim, Kyunghee AU - Kim K AD - Interdisciplinary Program of Nano-Medical Device Engineering, Hallym University, Chuncheon 24252, Korea. AD - Major in Materials Science and Engineering, Hallym University, Chuncheon 24252, Korea. FAU - Kim, Hyeju AU - Kim H AD - Major in Materials Science and Engineering, Hallym University, Chuncheon 24252, Korea. FAU - Sung, Gun Yong AU - Sung GY AUID- ORCID: 0000-0001-8515-4786 AD - Interdisciplinary Program of Nano-Medical Device Engineering, Hallym University, Chuncheon 24252, Korea. AD - Major in Materials Science and Engineering, Hallym University, Chuncheon 24252, Korea. AD - Integrative Materials Research Institute, Hallym University, Chuncheon 24252, Korea. LA - eng GR - NRF-2020R1A2C2009928/Ministry of Science ICT and Future Planning/ GR - HRF-202112-001/Hallym University/ PT - Journal Article DEP - 20220214 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (IL13 protein, human) RN - 0 (IL4 protein, human) RN - 0 (Interleukin-13) RN - 0 (Membrane Proteins) RN - 0 (loricrin) RN - 207137-56-2 (Interleukin-4) SB - IM MH - Animals MH - Dermatitis, Atopic/drug therapy/*metabolism MH - Eczema/drug therapy/metabolism/pathology MH - Epidermis/drug effects/metabolism/pathology MH - Gene Expression/drug effects/physiology MH - Humans MH - Inflammation/drug therapy/metabolism/pathology MH - Interleukin-13/*metabolism MH - Interleukin-4/*metabolism MH - Keratinocytes/drug effects/metabolism/pathology MH - Lab-On-A-Chip Devices MH - Membrane Proteins/pharmacology MH - Rats MH - Skin/drug effects/*metabolism/pathology PMC - PMC8878506 OTO - NOTNLM OT - atopic dermatitis OT - carbonic anhydrase II OT - human skin equivalent OT - interleukin-13 OT - interleukin-4 OT - skin-on-a-chip COIS- The authors declared no conflict of interest. EDAT- 2022/02/27 06:00 MHDA- 2022/03/15 06:00 PMCR- 2022/02/14 CRDT- 2022/02/26 01:07 PHST- 2022/01/13 00:00 [received] PHST- 2022/01/30 00:00 [revised] PHST- 2022/02/08 00:00 [accepted] PHST- 2022/02/26 01:07 [entrez] PHST- 2022/02/27 06:00 [pubmed] PHST- 2022/03/15 06:00 [medline] PHST- 2022/02/14 00:00 [pmc-release] AID - ijms23042116 [pii] AID - ijms-23-02116 [pii] AID - 10.3390/ijms23042116 [doi] PST - epublish SO - Int J Mol Sci. 2022 Feb 14;23(4):2116. doi: 10.3390/ijms23042116.