Statistical analysis. All analyses were performed using Prism 5 (GraphPad Software, La Jolla, CA). Statistical significance was determined using the two-way analysis of variance (ANOVA) test. The Interaction of LFA-1 on Mononuclear Cells and ICAM-1 on Tubular Epithelial Cells Accelerates TGF-β1-Induced Renal Epithelial-Mesenchymal Transition The epithelial-mesenchymal transition (EMT) of renal epithelial cells (RTECs) has pivotal roles in the development of renal fibrosis. Although the interaction of lymphocyte function-associated antigen 1 (LFA-1) on leukocytes and its ligand, intracellular adhesion molecule 1 (ICAM-1), plays essential roles in most inflammatory reactions, its pathogenetic role in the EMT of RTECs remains to be clarified. In the present study, we investigated the effect of the interaction of LFA-1 on peripheral blood mononuclear cells (PBMCs) and ICAM-1 on HK-2 cells after stimulation with TGF-β(1) on the EMT of RTECs. ICAM-1 was highly expressed in HK-2 cells. After TGF-β(1) stimulation, the chemokines CCL3 and CXCL12 increased on HK-2 cells. After co-culture of PBMCs and HK-2 cells pre-stimulated with TGF-β(1) (0.1 ng/ml) (HK-2-TGF-β(1) (0.1)), the expression of the active form of LFA-1 increased on PBMCs; however, total LFA-1 expression did not change. The expression of the active form of LFA-1 on PBMCs did not increase after co-culture with not CCL3 but CXCL12 knockdown HK-2-TGF-β(1) (0.1). The expression of epithelial cell junction markers (E-cadherin and occludin) further decreased and that of mesenchymal markers (vimentin and fibronectin) further increased in HK-2-TGF-β(1) (0.1) after co-culture with PBMCs for 24 hrs (HK-2-TGF-β(1) (0.1)-PBMCs). The phosphorylation of ERK 1/2 but not smad2 and smad3 increased in HK-2-TGF-β(1) (0.1)-PBMCs. The snail and slug signaling did not increase HK-2-TGF-β(1) (0.1)-PBMCs. Although the migration and invasion of HK-2 cells induced full EMT by a high dose (10.0 ng/ml) and long-term (72–96 hrs) TGF-β(1) stimulation increased, that of HK-2-TGF-β(1) (0.1)-PBMCs did not increase. These results suggested that HK-2 cells stimulated with TGF-β(1) induced conformational activation of LFA-1 on PBMCs by increased CXCL12. Then, the direct interaction of LFA-1 on PBMCs and ICAM-1 on HK-2 cells activated ERK1/2 signaling to accelerate the part of EMT of HK-2 cells induced by TGF-β(1.) Regardless of the underlying etiology, tubulointerstitial fibrosis is a common mechanism in the progression of chronic kidney disease (CKD) to end-stage renal disease [1, 2] . This progressive pathway involves interstitial infiltration by inflammatory mononuclear leukocytes [1, 3] . Integrin lymphocyte function-associated antigen 1 (LFA-1: a L b 2 integrin) is the predominant integrin on leukocytes and an important molecule in firm adhesion and migration of leukocytes to inflammatory sites [4, 5] . LFA-1 also plays pivotal roles as a signal transduction molecule by binding its ligand, namely, intracellular adhesion molecule 1 (ICAM-1) [6, 7] . Normally, LFA-1 is expressed in a low-affinity state for its ligand and, thus, cells do not make unnecessary adhesive contacts while in circulation [8, 9] . The affinity of LFA-1 for ICAM-1 is mediated by a conformational change of LFA-1 and they play essential roles in most inflammatory reactions [8, 9] . ICAM-1 has been reported to be expressed on renal tubular epithelial cells (RTECs) and the expression of ICAM-1 on RTECs was found to be associated with the infiltration of leukocytes in CKD [10, 11] . An experimental animal study showed that ICAM-1 was promptly up-regulated after renal injury and leukocyte infiltration subsequently occurred [12] . Kelly et al. reported that anti-ICAM-1 mAb mitigated leukocyte infiltration in tubulointerstitial space in an ischemic renal injury animal model [13] . Although these results suggested that ICAM-1 on RTECs and LFA-1 on leukocytes have some roles in the progression of renal diseases, the pathogenetic roles of their direct interaction in renal fibrosis remain unclear.