PMID- 38134557 OWN - NLM STAT- MEDLINE DCOM- 20240101 LR - 20240408 IS - 1096-0023 (Electronic) IS - 1043-4666 (Linking) VI - 174 DP - 2024 Feb TI - Anti-inflammatory effects of neuregulin-1 in HaCaT keratinocytes and atopic dermatitis-like mice stimulated with Der p 38. PG - 156439 LID - S1043-4666(23)00317-4 [pii] LID - 10.1016/j.cyto.2023.156439 [doi] AB - Neuregulin (NRG)-1 plays fundamental roles in several organ systems after binding to its receptors, ErbB2 and ErbB4. This study examines the role of NRG-1 in atopic dermatitis (AD), a chronic skin disease that causes dryness, pruritus, and inflammation. In mice administered Der p 38, the skin presents AD-like symptoms including filaggrin downregulation and infiltration of neutrophils and eosinophils. Noticeably, there is an increased expression of NRG-1, ErbB2, and ErbB4 in the skin. Upregulation of these proteins is significantly correlated to the clinical skin severity score. In human keratinocyte HaCaT cells, exposure to Der p 38 decreased filaggrin expression, and NRG-1 alone had no effect on the expression. However, co-treatment of Der p 38 with NRG-1 enhanced the filaggrin expression decreased by Der p 38. Pre-treatment with AG879 (an ErbB2 inhibitor) or ErbB4 siRNA blocked the recovery of filaggrin expression in the cells after co-treatment with Der p 38 and NRG-1. Der p 38 treatment enhanced the secretion of interleukin-6 (IL-6), IL-8, and monocyte chemoattractant protein-1 (MCP-1). Co-treatment of Der p 38 with NRG-1 lowered the cytokine secretion increased by Der p 38, although NRG-1 alone was not effective on cytokine alteration. Neutrophil apoptosis was not altered by NRG-1 or supernatants of cells treated with NRG-1, but the cell supernatants co-treated with Der p 38 and NRG-1 blocked the anti-apoptotic effects of Der p 38-treated supernatants on neutrophils, which was involved in the activation of caspase 9 and caspase 3. Taken together, we determined that NRG-1 has anti-inflammatory effects in AD triggered by Der p 38. These results will pave the way to understanding the functions of NRG-1 and in the future development of AD treatment. CI - Copyright (c) 2023. Published by Elsevier Ltd. FAU - Yun, Jeong Hee AU - Yun JH AD - Department of Biomedical Laboratory Science, College of Health Science, Eulji University, Uijeongbu 11759, Republic of Korea. FAU - Hong, Yujin AU - Hong Y AD - Department of Senior Healthcare, Graduate School, Eulji University, Uijeongbu 11759, Republic of Korea. FAU - Hong, Min Hwa AU - Hong MH AD - Department of Senior Healthcare, Graduate School, Eulji University, Uijeongbu 11759, Republic of Korea. FAU - Kim, Geunyeong AU - Kim G AD - Department of Senior Healthcare, Graduate School, Eulji University, Uijeongbu 11759, Republic of Korea. FAU - Lee, Ji-Sook AU - Lee JS AD - Department of Clinical Laboratory Science, Wonkwang Health Science University, Iksan 54538, Republic of Korea. FAU - Woo, Ran-Sook AU - Woo RS AD - Department of Anatomy and Neuroscience, Eulji University School of Medicine, Daejeon 34824, Republic of Korea. FAU - Lee, Juram AU - Lee J AD - Department of Biomedical Laboratory Science, College of Health Science, Eulji University, Uijeongbu 11759, Republic of Korea. FAU - Yang, Eun Ju AU - Yang EJ AD - Department of Biomedical Laboratory Science, Daegu Haany University, Gyeongsan 38610, Republic of Korea. Electronic address: ejyang@dhu.ac.kr. FAU - Kim, In Sik AU - Kim IS AD - Department of Biomedical Laboratory Science, College of Health Science, Eulji University, Uijeongbu 11759, Republic of Korea; Department of Senior Healthcare, Graduate School, Eulji University, Uijeongbu 11759, Republic of Korea. Electronic address: orientree@eulji.ac.kr. LA - eng PT - Journal Article DEP - 20231221 PL - England TA - Cytokine JT - Cytokine JID - 9005353 RN - 0 (Filaggrin Proteins) RN - 0 (Neuregulin-1) RN - 0 (Der p 38) RN - 0 (Cytokines) RN - EC 2.7.10.1 (Receptor, ErbB-4) RN - 0 (Anti-Inflammatory Agents) SB - IM MH - Mice MH - Animals MH - Humans MH - *Dermatitis, Atopic/genetics MH - Filaggrin Proteins MH - Neuregulin-1/pharmacology/metabolism/therapeutic use MH - Keratinocytes/metabolism MH - Skin/metabolism MH - Cytokines/metabolism MH - Receptor, ErbB-4/metabolism/pharmacology MH - Anti-Inflammatory Agents/pharmacology OTO - NOTNLM OT - Anti-inflammatory effect OT - Atopic dermatitis OT - Cytokine secretion OT - NRG-1 OT - Neutrophil apoptosis COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/12/22 19:43 MHDA- 2024/01/02 11:44 CRDT- 2023/12/22 18:10 PHST- 2023/07/25 00:00 [received] PHST- 2023/11/07 00:00 [revised] PHST- 2023/11/10 00:00 [accepted] PHST- 2024/01/02 11:44 [medline] PHST- 2023/12/22 19:43 [pubmed] PHST- 2023/12/22 18:10 [entrez] AID - S1043-4666(23)00317-4 [pii] AID - 10.1016/j.cyto.2023.156439 [doi] PST - ppublish SO - Cytokine. 2024 Feb;174:156439. doi: 10.1016/j.cyto.2023.156439. Epub 2023 Dec 21.