We previously showed that beta-defensin-1 (BD-1), an anti-microbial peptide, is up-regulated during progressive hyperglycemia in the kidneys of the GK rat [R.A. Page, C.A. Morris, J.D. Williams, C.J. von Ruhland, A.N. Malik, Isolation of diabetes-associated kidney genes using differential display, Biochem. Biophys. Res. Commun. 232 (1997) 49-53, R.A. Page, A.N. Malik, Elevated levels of beta-defensin-1 mRNA in diabetic kidneys of GK rats, Biochem. Biophys. Res. Commun. 310 (2003) 513-521]. In this paper, we show that human beta-defensin-1 (hBD-1) mRNA is directly up-regulated by glucose in cultured human renal cells. hBD-1 mRNA levels increased by similar to 7-fold and similar to 4-fold in human embryonic kidney (HEK) cells and human mesangial cells (HMC) grown in 25 mM glucose for four days, as determined by quantitative real-time PCR. Immunofluorescence showed that the hBD1 protein is located in the cytoplasm of HEK cells and transfected HMCs. The highest levels of hBD-1 mRNA were found in the kidney compared with 21 other human tissues. The increased expression of hBD-1 mRNA in cultured HMCs in high glucose suggests a role for hBD-1 in the molecular pathways induced during hyperglycemia. (c) 2006 Elsevier Inc. All rights reserved.