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J Bacteriol Virol. 2004 Mar;34(1):27-38. English. Original Article.
Bae EH , Park KW , Kim JW , Jang BC , Lim KJ , Jung TY , Kwon YK , Shin SW , Kim SP , Park JH , Kwon TK , Baek WK , Suh MH , Suh SI .
Hanbit Eye and laser center, #128-1 DeokSan Dong, Jung-Gu, Daegu, Korea.
Department of Microbiology, Chronic Disease Research Center, and Institute for Medical Science,School of Medicine Keimyung University, #194 DongSan-Dong, Jung-Gu, Daegu, Korea.
Department of Oriental Medicine, College of Oriental Medicine Daegu Haany University,#165 Sang-Dong, SooSung-Gu, Daegu, Korea.

Recently the transcriptional up-regulation of human beta-defensin 2 (HBD-2) by lipopolysaccharide (LPS) was found to be associated with NF-kappaB binding site. Although the general mechanisms of NF-kappaB activation by LPS stimulation are well understood, less is known about the signal transduction pathway leading to LPS-induced NF-kappaB activation in human corneal epithelial (HCE) cells. The aim of this study was to investigate the intracellular signals involved in LPS-induced HBD-2 mRNA expression in HCE cells. Pretreatments of inhibitors for NF-kappaB, protein tyrosine kinase, p38 mitogen activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK) attenuated the LPS-induced NF-kappaB DNA binding activity and HBD-2 mRNA expression. Furthermore, pretreatments with inhibitors for protein kinase C (PKC), phosphatidylcholine-phospholipase C, phosphatidylinositol-phospholipase C, or phosphatidate phosphohydrolase prevented LPS-induced HBD-2 mRNA expression and HBD-2 prmoter-driven luciferase activity. However, the increased expression of HBD-2 mRNA and the increased DNA binding activity of NF-kappaB induced by LPS were not changed by the blockage of extracellular signal-regulated kinase (ERK) and of addition of antioxidants. Forskolin, a protein kinase A (PKA) agonist did not induce HBD-2 mRNA expression. These data demonstrate that LPS-induced HBD-2 mRNA expression via NF-kappaB is, at least in part, dependent on PKC, p38 MAPK, JNK, and protein tyrosine kinase status, but appears to be independent on PKA, ERK and ROS in HCE cells. Taken together, there may be more than one signaling pathways that lead to LPS-induced up-regulation of HBD-2 mRNA expression in HCE cells.

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