PMID- 38339001 OWN - NLM STAT- MEDLINE DCOM- 20240214 LR - 20240228 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 25 IP - 3 DP - 2024 Jan 31 TI - Inhibiting Neutrophil Extracellular Traps Protects against Ultraviolet B-Induced Skin Damage: Effects of Hochu-ekki-to and DNase I. LID - 10.3390/ijms25031723 [doi] LID - 1723 AB - UV-B radiation induces sunburn, and neutrophils are pivotal in this inflammation. In this study, we examined the potential involvement of neutrophil extracellular traps (NETs) in ultraviolet B (UVB)-induced skin inflammation, correlating the skin inflammation-mitigating effects of Hochu-ekki-to on UV-B irradiation and NETs. To elucidate NET distribution in the dorsal skin, male ICR mice, exposed to UVB irradiation, were immunohistologically analyzed to detect citrullinated histone H3 (citH3) and peptidylarginine deiminase 4 (PAD4). Reactive oxygen species (ROS) production in the bloodstream was analyzed. To establish the involvement of NET-released DNA in this inflammatory response, mice were UV-B irradiated following the intraperitoneal administration of DNase I. In vitro experiments were performed to scrutinize the impact of Hochu-ekki-to on A23187-induced NETs in neutrophil-like HL-60 cells. UV-B irradiation induced dorsal skin inflammation, coinciding with a significant increase in citH3 and PAD4 expression. Administration of DNase I attenuated UV-B-induced skin inflammation, whereas Hochu-ekki-to administration considerably suppressed the inflammation, correlating with diminished levels of citH3 and PAD4 in the dorsal skin. UV-B irradiation conspicuously augmented ROS and hydrogen peroxide (H(2)O(2)) production in the blood. Hochu-ekki-to significantly inhibited ROS and H(2)O(2) generation. In vitro experiments demonstrated that Hochu-ekki-to notably inhibited A23187-induced NETs in differentiated neutrophil-like cells. Hence, NETs have been implicated in UV-B-induced skin inflammation, and their inhibition reduces cutaneous inflammation. Additionally, Hochu-ekki-to mitigated skin inflammation by impeding neutrophil infiltration and NETs in the dorsal skin of mice. FAU - Inaba, Issei AU - Inaba I AD - Department of Biochemistry, Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, 3500-3, Minamitamagaki, Suzuka 513-8670, Japan. FAU - Hiramoto, Keiichi AU - Hiramoto K AD - Department of Biochemistry, Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, 3500-3, Minamitamagaki, Suzuka 513-8670, Japan. FAU - Yamate, Yurika AU - Yamate Y AD - Department of Biochemistry, Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, 3500-3, Minamitamagaki, Suzuka 513-8670, Japan. FAU - Morita, Akihiro AU - Morita A AD - Department of Biochemistry, Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, 3500-3, Minamitamagaki, Suzuka 513-8670, Japan. FAU - Tsutsumi, Tomonari AU - Tsutsumi T AD - Department of Biochemistry, Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, 3500-3, Minamitamagaki, Suzuka 513-8670, Japan. FAU - Yasuda, Hiroyuki AU - Yasuda H AD - Division of Pathological Sciences, Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Misasagi 5, Yamashina, Kyoto 607-8414, Japan. FAU - Sato, Eisuke F AU - Sato EF AD - Department of Biochemistry, Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, 3500-3, Minamitamagaki, Suzuka 513-8670, Japan. LA - eng GR - JP22K11790/Japan Society for the Promotion of Science/ PT - Journal Article DEP - 20240131 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (bu-zhong-yi-qi-tang) RN - 37H9VM9WZL (Calcimycin) RN - EC 3.1.21.1 (Deoxyribonuclease I) RN - 0 (Drugs, Chinese Herbal) RN - 0 (Histones) RN - BBX060AN9V (Hydrogen Peroxide) RN - EC 3.5.3.15 (Protein-Arginine Deiminases) RN - 0 (Reactive Oxygen Species) SB - IM MH - Animals MH - Male MH - Mice MH - Calcimycin/pharmacology MH - *Deoxyribonuclease I/pharmacology/metabolism MH - *Drugs, Chinese Herbal MH - *Extracellular Traps/drug effects/radiation effects MH - Histones/metabolism MH - Hydrogen Peroxide/metabolism MH - Inflammation/metabolism MH - Mice, Inbred ICR MH - Neutrophils/metabolism MH - Protein-Arginine Deiminases/metabolism MH - Reactive Oxygen Species/metabolism MH - *Ultraviolet Rays/adverse effects PMC - PMC10855064 OTO - NOTNLM OT - Hochu-ekki-to OT - NETosis OT - UV-B irradiation OT - histone citrullination OT - inflammation OT - neutrophil extracellular trap COIS- The authors declare no conflicts of interest. EDAT- 2024/02/10 10:44 MHDA- 2024/02/10 14:47 PMCR- 2024/01/31 CRDT- 2024/02/10 01:12 PHST- 2023/12/28 00:00 [received] PHST- 2024/01/26 00:00 [revised] PHST- 2024/01/29 00:00 [accepted] PHST- 2024/02/10 14:47 [medline] PHST- 2024/02/10 10:44 [pubmed] PHST- 2024/02/10 01:12 [entrez] PHST- 2024/01/31 00:00 [pmc-release] AID - ijms25031723 [pii] AID - ijms-25-01723 [pii] AID - 10.3390/ijms25031723 [doi] PST - epublish SO - Int J Mol Sci. 2024 Jan 31;25(3):1723. doi: 10.3390/ijms25031723.