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Silent HMGB1 Alleviates LPS or IL-17A Induced Inflammation and Apoptosis of Human Middle Ear Epithelial Cells via Inhibiting p38 MAPK Signaling Pathway |
ABULAJIANG Tuoheti, ABULIKEMU Yi, UUMAIER Yasheng, et al |
Xinjiang Uygur Autonomous Region People's Hospital, Xinjiang Urumqi 830001, China |
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Abstract Objective: To investigate the regulatory effects and mechanisms of high-mobility group protein B1 (HMGB1) on the inflammatory response and apoptosis of human middle ear epithelial cells (HMEECs) induced by lipopolysaccharide (LPS) or interleukin-17A (IL-17A). Methods: HMEEC cell line was cultured. HMEECs were divided into the control group, LPS group, LPS+shRNA negative control group (LPS+shNC group), LPS+shRNA-mediated HMGB1 knockdown group (LPS+shHMGB1 group), LPS+p38 mitogen-activated protein kinase (p38 MAPK) inhibitor SB202190 group (LPS+SB202190 group), IL-17A group, IL-17A+shNC group, IL-17A+shHMGB1 group, and IL-17A+SB202190 group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the changes in the levels of TNF-α, IL-1β and IL-6. Western blot was used to detect the expression of mucin 5AC (MUC5AC), mucin 8 (MUC8), p38 MAPK, phosphorylated p38 MAPK (p-p38 MAPK), E-twenty-six like 1 protein (ELK1), B-cell lymphoma 2 protein (Bcl-2), and Bcl-2 associated X protein (Bax). Flow cytometry was used to detect cell apoptosis. Results: Compared with the control group, the apoptosis rate of HMEECs in the LPS group or IL-17A group was increased, and the expression levels of HMGB1, MUC5AC, MUC8, TNF-α, IL-1β, IL-6, p38, p-p38, ELK1, and Bax were increased, while the expression level of Bcl-2 was decreased (all P<0.05). Compared with the LPS group or IL-17A group, the apoptosis rate was decreased in the LPS+shHMGB1 group or IL-17A+shHMGB1 group, and the expression levels of HMGB1, MUC5AC, MUC8, TNF-α, IL-1β, IL-6, p38, p-p38, ELK1, and Bax were all decreased, while the expression level of Bcl-2 was increased (all P<0.05). Compared with the LPS group or IL-17A group, the apoptosis rate was decreased in the LPS+SB202190 group or IL-17A+SB202190 group, and the expression levels of MUC5AC, MUC8, TNF-α, IL-1β, IL-6, p38, p-p38, ELK1, and Bax were all decreased, while the expression level of Bcl-2 was increased (all P<0.05). Conclusion: Silent HMGB1 alleviates LPS or IL-17A-induced inflammation and apoptosis of HMEECs via inhibiting p38 MAPK signaling pathway.
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[1] Tanz RR.Otitis media stewardship:who wants it[J].Pediatric Infect Dis Soc,2023,12(1):8-9. [2] Jung SY,Kim D,Park DC,et al.Immunoglobulins and transcription factors in otitis media[J].Int Mol Sci,2021,22(6):3201. [3] Goldman RD.Acute otitis media in children 6 months to 2 years of age[J].Can Fam Physician,2022,68(8):589-590. [4] Parrino D,Val M,Lovato A,et al.Pediatric temporomandibular joint ankylosis and arthritis:forgotten complications of acute otitis media[J].Am Otolaryngol,2022,43(5):103599. [5] Chen R,Zou J,Zhong X,et al.HMGB1 in the interplay between autophagy and apoptosis in cancer[J].Cancer Lett,2024(581):216494. [6] Chen LL,Morcelle C,Cheng ZL,et al.Itaconate inhibits TET DNA dioxygenases to dampen inflammatory responses[J].Nat Cell Biol,2022,24(3):353-363. [7] Skrzypczak-Wiercioch A,Satat K.Lipopolysaccharide-induced model of neuroinflammation:Mechanisms of action,research application and future directions for its use[J].Molecules,2022,27(17):5481. [8] Pandiyan P,McCormick TS.Regulation of IL-17A-producing cells in skin inflammatory disorders[J].Invest Dermatol,2022,142(3):867-875. [9] Tuczak MW,Dzaman K,Zarebat,et al.HMGB1 carried by small extracellular vesicles potentially plays a role in promoting acquired middle ear cholesteatoma[J].Diagnostics (Basel),2023,13(22):3469. [10] Lin Z,Li P,Tang Y,et al.Hsa_circ_0007292 promotes chondrocyte injury in osteoarthritis via targeting the miR-1179/HMGB1 axis[J].Orthop Surg Res,2023,18(1):544. [11] He R,Chen Y,Chen X,et al.Mechanism of miR-181a-5p in regulatory T/T-helper 17 immune imbalance and asthma development in mice with allergic rhinitis[J].Int Arch Allergy Immunol,2022,183(4):375-388. [12] Li M,Li Z,Ma X,et al.Huangqi guizhi wuwu decoction can prevent and treat oxaliplatin-induced neuropathic pain by TNFα/IL-1β/IL-6/MAPK/NF-kB pathway[J].Aging (Albany NY),2022,14(12):5013-5022. [13] Huang YK,Chang KC,Li CY,et al.AKR1B1 represses glioma cell proliferation through p38 MAPK-mediated Bcl-2/BAX/Caspase-3 apoptotic signaling pathways[J].Curr Issues Mol Biol,2023,45(4):3391-3405. [14] Ko YS,Gi EJ,Lee S,et al.Dual red and near-infrared light-emitting diode irradiation ameliorates LPS-induced otitis media in a rat model[J].Front Bioeng Biotechnol,2023(11):1099574. [15] Alaaeldin R,Bakkar SM,Mohyeldin RH,et al.Azilsartan modulates HMGB1/NF-κB/p38/ERK1/2/JNK and apoptosis pathways during renal ischemia reperfusion injury[J].Cells,2023,12(1):185. |
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