Anti-inflammatory effects of neuregulin-1 in HaCaT keratinocytes and atopic dermatitis-like mice stimulated with Der p 38

• Published in: Cytokine (Philadelphia, Pa.) Vol. 174; p. 156439
• Main Authors: Yun, Jeong Hee, Hong, Yujin, Hong, Min Hwa, Kim, Geunyeong, Lee, Ji-Sook, Woo, Ran-Sook, Lee, Juram, Yang, Eun Ju, Kim, In Sik
• Format: Journal Article
• Language: English
• Published: England 01.02.2024
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Cytokines - metabolism; Dermatitis, Atopic - genetics; Filaggrin Proteins; Humans; Keratinocytes - metabolism; Mice; Neuregulin-1 - metabolism; Neuregulin-1 - pharmacology; Neuregulin-1 - therapeutic use; Receptor, ErbB-4 - metabolism; Receptor, ErbB-4 - pharmacology; Skin - metabolism; Neutrophil apoptosis; Anti-inflammatory effect; Cytokine secretion; Atopic dermatitis; NRG-1
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2023.156439

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.