TY - JOUR AB - A humanized anti‑Toll‑like receptor 4 (TLR4) monoclonal antibody (mAb) was previously produced using phage antibody library technology, and it was found that the mAb could effectively ameliorate lipopolysaccharide (LPS)‑induced damage in macrophages. The present study investigated the protective effects exerted by the humanized anti‑TLR4 mAb against LPS‑induced acute kidney injury (AKI), as well as the underlying mechanisms. Female C57BL/6 mice were randomly divided into four groups (n=8 per group): i) Control; ii) LPS; iii) LPS + humanized anti‑TLR4 mAb (1 µg/g); and iv) LPS + humanized anti‑TLR4 mAb (10 µg/g). Serum creatinine, blood urea nitrogen, IL‑6, TNFα and IL‑1β levels were then examined, followed by renal pathology assessment, immunohistochemical staining, reverse transcription‑quantitative PCR and western blotting to assess apoptosis/survival/inflammation‑related molecules and kidney injury molecule (KIM)‑1. The humanized anti‑TLR4 mAb successfully ameliorated LPS‑induced AKI and renal pathological damage. The humanized anti‑TLR4 mAb also dose‑dependently suppressed LPS‑induced elevations in serum IL‑6, TNFα and IL‑1β, and decreased the renal expression levels of myeloid differentiation primary response 88 (MyD88), IKKα/β, IκB, p65 and KIM‑1. Compared with the LPS group, renal Bax and KIM‑1 expression levels were significantly downregulated, and Bcl‑2 expression was notably upregulated by the humanized anti‑TLR4 mAb. Moreover, the humanized anti‑TLR4 mAb also significantly decreased the protein expression levels of MyD88, phosphorylated (p)‑IKKα/β, p‑IκB and p‑p65 in the renal tissues compared with the LPS group. Therefore, the present study indicated that the anti‑inflammatory effects of the humanized anti‑TLR4 mAb against LPS‑related AKI in mice were mediated via inhibition of the TLR4/NF‑κB signaling pathway. AD - Department of Nephrology, The Affiliated Wuxi No.2 People's Hospital of Nanjing Medical University, Wuxi, Jiangsu 214000, P.R. China Department of Nephrology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu 214023, P.R. China Key Laboratory of Antibody Technique of Ministry of Health, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China AU - Zhang,Qiuhua AU - Wang,Liang AU - Wu,Mian AU - Liu,Xiaobin AU - Zhu,Yushan AU - Zhu,Jin AU - Xing,Changying DA - 2021/08/01 DO - 10.3892/mmr.2021.12245 IS - 2 JO - Mol Med Rep KW - humanized anti‑TLR4 mAb acute kidney injury NF‑κB TLR4/LPS PY - 2021 SN - 1791-2997 1791-3004 SP - 608 ST - Humanized anti‑TLR4 monoclonal antibody ameliorates lipopolysaccharide‑related acute kidney injury by inhibiting TLR4/NF‑κB signaling T2 - Molecular Medicine Reports TI - Humanized anti‑TLR4 monoclonal antibody ameliorates lipopolysaccharide‑related acute kidney injury by inhibiting TLR4/NF‑κB signaling UR - https://doi.org/10.3892/mmr.2021.12245 VL - 24 ER -