The present study showed that the TGF-b 1 -induced EMT on HK-2 cells was accelerated by PBMCs. The decrease of expression level of epithelial cell junction markers and increase of expression level of mesenchymal markers on HK-2 cells after stimulation of TGF-b 1 were accelerated by co-culture with PBMCs. These EMT marker changes on HK-2 cells were mitigated by anti-LFA-1 mAb or anti-ICAM-1 mAb. These results demonstrated that the direct interaction of LFA-1 on PBMCs and ICAM-1 on HK-2 cells contributed to accelerate TGF-b 1 -induced EMT on HK-2 cells. HK-2 cells stimulated by TGF-b 1 induced conformational activation of LFA-1 on PBMCs; however, HK-2 cells without stimulation by TGF-b 1 or TGF-b 1 alone did not induce conformational activation of LFA-1 on PBMCs. The locally secreted chemokines can trigger integrin-dependent adhesion of circulating leukocytes that leads to infiltration [19, 20, 21, 22] . Several studies have characterized the expression pattern of chemokines in animal models of tubulointerstitial disease [23, 24, 25] . They demonstrated that various chemokines such as CCL2, CCL3, CCL4 and CCL5 are expressed only in the diseased compartment of the kidney and renal chemokine expression has been found to correlate with the leukocyte accumulation area and renal damage [23, 24, 25, 26] . On the basis of these findings, we investigated the regulation of the chemokines that may mediate LFA-1 activation of PBMCs on HK-2 cells by the stimulation of TGF-b 1 . CCL2 decreased on HK-2 cells by stimulation of TGF-b 1. This result was consistent with a previous study [27] . CCL3 and CXCL12 increased on HK-2 cells by TGF-b 1 stimulation. CCL21 did not change on HK-2 cells by TGF-b 1 stimulation. CCL3, CCL4, CCL17, CCL19, CCL20 and CCL22 were not detected on HK-2 cells either before or after TGF-b 1 stimulation. CCL3 and CXCL12 were reported to activate LFA-1 on both monocytes and lymphocytes [28, 29, 30, 31, 32] . In the present study, not CCL3 but CXCL 12 contributed to induction of the conformational activation of LFA-1 on PBMCs, because less AL57-positive cells were detected among PBMCs after co-culture with CXCL12 knockdown HK cells compared with those among Mock, CCL3 knockdown and control knockdown HK-2 cells pre-stimulated with TGF-b 1. Furthermore, the EMT marker changes of HK-2 cells pre-stimulated with TGFb 1 and morphological changes upon co-culture with PBMC were inhibited by CXCL12 knockdown on HK-2 cells (Figures S2 and  S3 ). These results suggested that CXCL12 was a key chemokine for EMT of RTECs that induced TGF-b 1 accelerated by PBMCs.