3b). However, the blocking of CD80 on TLR-7-activated PDC reduced their capacity to stimulate T cell proliferation by ±15% and completely

abrogated the increase in T cell stimulatory ability of rapamycin-treated TLR-7-activated PDC, indicating that this is caused by the enhanced Ponatinib purchase CD80 expression. Blockade of IFN-αR2 did not abrogate the difference in ability between rapamycin-treated and non-rapamycin-treated PDC to stimulate cytokine secretion by T cells, indicating that this was not due to reduced IFN-α production by rapamycin-treated PDC. Together, these data show that, on one hand, rapamycin promotes the ability of TLR-7-activated PDC, but not of TLR-9-activated PDC, to stimulate CD4+ memory T cell and CD4+ naive T cell proliferation by increasing their expression LDE225 of CD80,

but on the other hand inhibits the capacity of PDC to stimulate cytokine production by mainly naive T cells. Activated human PDC can stimulate the generation of CD4+FoxP3+ Treg from naive CD4+ T cells [3, 6, 7]. Previously, we have shown that human PDC induce the generation of alloantigen-specific CD8+CD38+LAG-3+CTLA-4+ Treg from allogeneic CD3+ T cells, and that activation of PDC by TLR ligation enhances their ability to generate CD8+ Treg [8]. Here, we determined whether or not rapamycin affects the ability of TLR-7-activated Exoribonuclease PDC to generate CD4+ and CD8+ Treg. Seven-day co-cultures of CFSE-stained naive or memory CD3+ T cells with TLR-7 activated allogeneic PDC resulted in CD4+ T cells with high FoxP3 expression within

the proliferating (CFSE-low) cells. Treatment of PDC with rapamycin enhanced their capacity to induce CD4+FoxP3+ Treg in the proliferating cells in the naive Th compartment (Fig. 4a,b). Because, after culture, many CD4+FoxP3– cells expressed CD25 (Fig. 4a) and CD127 expression was up-regulated on CD4+FoxP3+ T cells generated during these cultures (data not shown), it was not possible to purify CD4+FoxP3+ Treg after culture in order to determine their suppressive function. Seven-day co-cultures of CD3+ T cells with loxoribine-stimulated PDC resulted in 32 ± 7% of CD8+ T cells showing the regulatory CD38+LAG3+ phenotype, while co-cultures with rapamyin-treated loxoribine-stimulated PDC generated 25 ± 3% CD38+LAG3+ Treg within total CD8 T cells (Fig. 4c). In absolute numbers, the addition of rapamycin to PDC during their activation with loxoribine did not significantly affect the yield of CD8+CD38+LAG3+ Treg at the end of the cultures (Fig. 4d). In addition, the suppressive function of the CD8+ Treg was not affected by rapamycin (Fig. 4e). Thus, rapamycin treatment of TLR-7-stimulated PDC enhances their capacity to induce CD4+FoxP3+ Treg, but does not affect their capacity to generate CD8+CD38+LAG3+ Treg.

Fas deficiency in the NOD/SCID recipients addressed the requirement of Fas expression by CD4+ T cells alone to cause diabetes, Fas deficiency on APCs should not interfere with antigen

presentation. FasL deficiency (gld) in the NOD/SCID recipients ensures that the only source of FasL are the transferred activated CD4+ T cells. Mice sufficient for Fas were significantly more susceptible to diabetes development upon CD4+ Ku-0059436 mw T-cell transfer than Fas-deficient recipients (47 and 6% respectively, p<10−3 log-rank test) (Fig. 1). Our experiments demonstrate that primed CD4+ T cells require the Fas-death receptor pathway on recipients, presumably in the pancreatic β-cell compartment, to mediate their diabetogenic action Torin 1 (Fig. 1). We tested whether transgenically expressed FasL on β cells accelerated the Fas-mediated β-cell death by CD4+ T cells. Two types of splenic CD4+ T cells were used for these experiments, either from diabetic (detectable glycosuria and glycemia above 200 mg/dL) or non-diabetic (not exhibiting glycosuria) NOD female donors, and 12.5 million of CD4+ T cells were transferred per recipient. The recipient mice were

FasL-sufficient NOD/SCID females and either transgene positive or negative for the RIP-FasL transgene (Fig. 2) (Table 1). Interestingly, mice expressing the FasL transgene on β cells that received CD4+ T cells from a diabetic donor exhibit a certain trend, although not significant (p=0.059 log-rank test), to develop delayed diabetes compared with transgene-negative littermates (at day 107 post-transfer 57% (4/7) of transgene-positive recipients developed diabetes compared with 100% (5/5) of transgene-negative littermates) (Fig. 2A). In contrast,

when spleen CD4+ 6-phosphogluconolactonase T cells from a non-diabetic donor female were transferred, no differences in either cumulative incidence or kinetics of disease were found between transgene-negative or -positive recipients (p>0.9, log-rank test) (Fig. 2B; Table 1). The difference between these two results (Fig. 2A and B) may be due to the fact that fully activated islet-specific CD4+ T cells from a diabetic donor are more susceptible to Fas-induced apoptosis upon engagement with FasL 28. This tendency to develop a higher incidence of diabetes that was detected in recipient mice that do not overexpress FasL on β cells could suggest a state of immune privilege towards immune attack by activated islet-antigen-specific CD4+ T cells as is suggested in Fig. 2B. IL-1β is one of the key pro-inflammatory cytokines believed to upregulate Fas in the course of T1D development. Caspase 1, also known as IL-1 converting enzyme, is responsible for processing the immature pro-cytokines IL-1 and IL-18 into their corresponding mature cytokine forms 29. NOD mice deficient for caspase 1 develop autoimmune diabetes normally (p>0.9, log-rank test) (Fig. 3), which has also been described in another report 30.

Niban decreased in renal cortex of UUO rats and transforming growth factor-β1 (TGF-β1)-stimulated HK-2 cells. siRNA of Niban increased apoptosis of HK-2 cells. TGF-β1 also increased apoptosis of HK-2 cells. Overexpression of Niban failed to diminish apoptosis of HK-2 cells induced by TGF-β1. Niban decreased in renal tubular cells of patients of obstructive nephropathy, UUO rats and TGF-β1 stimulated HK-2 cells. Suppressing Niban increases apoptosis in HK-2 cells. Niban may be associated with apoptosis of HK-2 cells. “
“Adenoviruses are common pathogens that have the potential to cause opportunistic infections with significant

morbidity and mortality in immunocompromised hosts. The significance of adenoviral infection and disease is incompletely known in the setting of kidney transplantation. Reported adenovirus Talazoparib cost infections in renal transplant recipients have typically manifested as haemorrhagic cystitis and tubulointerstitial nephritis. Pneumonia, hepatitis and enteritis are often seen in other solid organ recipients. However, disseminated or severe adenovirus infections, including fatal cases, have been described in renal transplant recipients. There is uncertainty regarding monitoring and treatment of this virus. Although not supported by randomized clinical trials, cidofovir is used for the treatment of adenovirus

disease not responding to reduction of immunosuppression. We present a case series of 2 patients with disseminated adenovirus infection in our centre who presented at different times from the time of transplantation. The patient is a 70-year-old click here female with background of adult polycystic kidney disease (APKD), who received her first kidney transplant from a deceased donor in 2009. She was maintained on prednisolone (10 mg), tacrolimus (1 mg twice daily) and mycophenolate mofetil (500 mg twice daily). She presented to the hospital 27 months after kidney Amylase transplant with chills, rigors and fever up to 39.6°C

for the previous 6 days. Subsequently she had loose, watery stool and haematuria. All basic septic screens at initial presentation were unremarkable. She was started on broad spectrum antibiotic with no significant improvement. Subsequently her urine, stool, blood culture and respiratory secretion were positive for adenovirus assessed by polymerase chain reaction (PCR). All her immunosuppression was withheld except for prednisolone. She deteriorated clinically requiring ICU admission for haemodynamic instability with new onset atrial fibrillation (AF). Gradually her renal function declined from her baseline creatinine of 115 μmol/L and peaked at 232 μmol/L. She was treated with Cidofovir 3 mg/kg weekly for 3 weeks. Her kidney was subsequently biopsied which showed moderate interstitial infiltrates with moderate to severe tubulitis. No inclusion viral bodies were seen on light or electron microscopy. Immunofluorescence was negative for C4d.

Following microscopic inspection, the 134 cases were assigned to one of the four pathological phenotypes according to the varying forms and distribution of Aβ deposition (as SP and/or CAA) within frontal, temporal and occipital lobes, and coded accordingly Roxadustat (see methods for criteria) (Figure 1). However, there was often heterogeneity in phenotypic presentation across the three regions in individual cases. In some cases, all three regions showed

a similar histological phenotype, whereas in others there were regional variations with the frontal and temporal cortex closely resembling each other histologically though being dissimilar to occipital cortex, nearly always with respect to the presence/distribution of CAA. Hence, 35 cases (coded 111) showed type 1 pathology within all three regions (that is, Aβ deposition predominantly as SP with or without CAA, AZD6244 datasheet and involving only superficial (leptomeningeal) blood vessels) (red in Figure 2). Sixty-eight cases (coded 112, 122, 212 or 222) showed type 2 pathology with Aβ deposition as SP and CAA in leptomeningeal and deeper intracortical vessels,

in the occipital lobe: dyshoric change was often evident surrounding affected vessels (green in Figure 2). Sometimes, similar changes were also seen in frontal but not temporal cortex (where type 1 change was present, and coded 212 or 122 respectively), or type 1 changes were only seen in both regions (and coded 112). Twenty cases showed type 3 pathology in all three regions (and coded 333) with robust CAA predominantly within capillaries in the occipital lobe, and leptomeningeal and/or intracortical CAA in frontal and/or temporal region (and coded 113, 123, 213, 223 or 323) (blue in Figure 2). In these cases, within occipital lobe SP were absent or relatively few, though were usually much more numerous in frontal and temporal lobes. Four cases (coded 214,

224 or 444) showed type 4 pathology with a predominant CAA phenotype, where Aβ was heavily deposited in the leptomeningeal and cortical vessels, but not capillaries, within occipital lobe (and sometimes also in frontal and temporal Ergoloid lobes): dyshoric change was always evident surrounding the vessels. Aβ deposition, as SP, in occipital lobe was absent or infrequent (orange in Figure 2). For group comparisons, cases were pooled according to the type of histological presentation within the occipital lobe, irrespective of whether changes in frontal and temporal lobe always followed suit. Nonetheless, there were seven cases (coded 121, 211 or 221) which formed an ‘outlier’ group within type 2 pathology (purple in Figure 2). These were differentiated from the other cases with type 2 pathology by virtue of the fact that there was intracortical CAA in frontal and/or temporal cortex but, in contrast to the other cases in that group, these were without occipital involvement.

After adjustment, candidemia was strongly associated with duration of total [duration > 7 days: OR = 20.09; 95% confidence interval (CI): 3.44–117.52] and peripheral parenteral nutrition (duration > 7 days: OR = 26.83; 95% CI: 6.54–110.17), other central vascular catheters (OR = 5.17; 95% CI: 1.24–23.54) and glycopeptide antibiotics (OR = 6.45; 95% CI: 1.90–21.91). Duration of peripheral and total parenteral

nutrition and antibiotics predicted over 50% of all candidemias. Intervention studies should be planned to evaluate effectiveness of candidemia Alvelestat molecular weight prevention by restricting parenteral nutrition, prompting earlier enteral feeding, and reducing use of antibiotics, especially glycopeptides, in elderly patients. “
“Candidiasis

accounts for 10–20% of bloodstream infections in paediatric intensive care units (PICUs) and a significant increase in morbidity, mortality, and length of hospital stay. Enteric colonisation by Candida species is one of the most important risk factor for invasive candidiasis. The local defence mechanisms may be altered in critically ill patients, thus facilitating Candida overgrowth and candidiasis. Systemic antifungals have been proven to be effective in reducing fungal colonisation and invasive fungal infections, but their use is not without harms. Early restoration or maintenance of intestinal microbial flora using probiotics could be one of the important tools for reducing Candida infection. A few studies have demonstrated that probiotics are able to prevent Candida growth and colonisation Selleckchem PF01367338 in neonates, whereas their role in preventing invasive candidiasis in such patients is still unclear. Moreover, there are no published data on role of probiotics supplementation in the prevention of candidiasis

in critically ill children beyond neonatal period. There are gap in our knowledge regarding efficacy, cost Cyclooxygenase (COX) effectiveness, risk-benefit potential, optimum dose, frequency and duration of treatment of probiotics in prevention of fungal infections in critically ill children. Studies exploring and evaluating the role of probiotics in prevention of Candida infection in critically ill children are needed. “
“Candidemia is the most frequent manifestation observed with invasive candidiasis. The aim of this study was to analyse the trends of candidemia in a large tertiary-care hospital to determine the overall incidence during January 1996–December 2012, as well as to determine the susceptibility of 453 isolates according to the revised Clinical and Laboratory Standards Institute (CLSI) breakpoints. Candidemia episodes in adult and paediatric patients were retrospectively analysed from the laboratory data of Uludağ University Healthcare and Research Hospital.

To investigate whether the PS-5 mimetic affects the migratory property of T lymphocytes, we analyzed the ability

of T-cell populations to respond to supernatants from IFN-γ-activated keratinocytes in transwell migration assays. As shown in Figure 5A, supernatants from untreated or NC-treated-keratinocytes stimulated Sorafenib concentration with IFN-γ were fourfold more efficient in eliciting migratory responses of circulating PBMCs previously stained for anti-CD3, compared with supernatants from unstimulated strains. On the contrary, the treatment with PS-5, as well as with KIR peptide, significantly reduced the IFN-γ-dependent migration of PBMCs toward the supernatants of activated keratinocytes. Similar effects were observed in migration experiments performed with skin T-cell lines derived from type 1-mediated inflammatory skin diseases, including psoriasis (Fig. 5B) and lichen planus (Fig. 5C). Finally, we investigated the effects of PS-5 peptide on STAT1 activation and the expression of STAT1-dependent inflammatory genes in organ cultures of normal human skin treated with IFN-γ. As shown in Figure 6, the explants of IFN-γ-treated skin preincubated with PS-5, as well as with KIR peptide, showed a faint epidermal immunoreactivity for phosphorylated STAT1, compared with those observed in skin explants treated with NC peptide or its vehicle (Fig. 6). In these skin explants, phospho-STAT1 expression

BAY 80-6946 order was comparable with that observed in abundance in lesional skin obtained from psoriatic patients, used as positive control. In contrast, phospho-STAT1 staining was quite absent in untreated skin explants and in uninvolved zones (nonlesional skin) of psoriatic plaques. As direct consequence of the reduced STAT1 phosphorylation and activation, the Edoxaban epidermal expression of ICAM-1, HLA-DR, CXCL10 was abrogated in IFN-γ-treated explants of human skin incubated with PS-5 or KIR mimetics, compared with that found in organ cultures treated with NC peptide or vehicle (Fig. 7). The decrease of the number of ICAM-1+,

HLA-DR+, or CXCL10+ epidermal cells in PS-5-treated skin organ cultures was highly significant, as demonstrated by counting positive cells/mm2 in four different stained sections obtained from three skin explants for each condition (Fig. 7). Taken together, these results highlighted the efficiency of PS-5 mimetic to dampen the inflammatory responses triggered by JAK2/STAT1 signaling in human skin. Inhibition of JAK2 activity and the consequent inactivation of the downstream STAT1 transcription factor represent a promising strategy for the attenuation of the inflammatory responses elicited by epidermal keratinocytes following massive exposure to IFN-γ in the skin. In recent years, a number of small molecule inhibitors of IFN-γ signaling have been developed, including mimetics sharing the KIR region of SOCS1 protein [12, 22, 23].

The epidermis

also contains some immune cells, including Langerhans cells and CD8+ T cells, while the underlying dermis exhibits a more complicated histology due to the presence of a variety of immune cells, such as CD4+ Th cells, MΦs, and DC, in addition to fibroblasts 1. CD4+ Th cells can be classified into at least four subsets: Th1, Th2, Th17, and Treg, which coordinate immunity selleck screening library by producing unique sets of cytokines 2, 3. They are derived from naïve CD4+ T cells through exposure to specific cytokines and antigen presentation by DC 1, 3. IFN-γ and IL-4 promote the development of Th1 and Th2 cells, respectively, and Th1 and Th2 cells produce IFN-γ and IL-4, respectively, as their signature cytokines. On the other hand, Th17 cells are derived in the presence of TGF-β plus IL-6 for mice or TGF-β plus IL-21 for humans and produce IL-17 3, 4. They also produce IL-22 when

stimulated with IL-23 4. High concentration of TGF-β results in induction of the transcription factor Foxp3 and promotes the development of Treg, ACP-196 nmr which negatively regulate immune responses through production of IL-10 3, 5. Deregulated cytokine production in the skin leads to inflammatory diseases exemplified by psoriasis and atopic dermatitis in humans, which are T-cell-mediated skin diseases with unknown origin 6, 7. Cytokines derived from Th1 and Th17 cells are implicated in the pathogenesis of psoriasis, while those from Th2 cells are implicated in the pathogenesis of atopic dermatitis 8, 9. Moreover, cytokines derived from keratinocytes are recognized to have an important pathogenic role. For

instance, IL-23 is highly produced by epidermal keratinocytes as well as by Langerhans cells, dermal DC, and MΦs 10, and is implicated in the pathogenesis of psoriasis 1, 7. In addition, keratinocytes release not only chemokines exemplified by CC chemokine ligand (CCL)-20, a chemoattractant for DC precursors 11, but also a large amount of peptides exemplified by LL-37 12 and S100A7 (also known as psoriasin) 13, which are implicated not in the pathogenesis of psoriasis. Phosphoinositide-specific phospholipase C (PLC) catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate into two vital second messengers, diacylglycerol and inositol 1,4,5-trisphosphate, thereby playing a pivotal role in intracellular signaling. There are six families of mammalian PLC isoforms (β, γ, δ, ε, ζ,and η) 14. PLCε was first identified by others and us as a direct downstream effector of Ras family small GTPases: Ras, Rap1, and Rap2 14, 15. In the skin, PLCε is expressed in resident skin cells but not in leukocytes 16–18. By using PLCε−/− mice, in which PLCε was inactivated by gene targeting, we showed that PLCε plays a crucial role in cutaneous carcinogenesis and inflammation.

KIR3DS1(3DS1/3DL1) could have a greater effect on protection against HIV-1 infection in HESN patients when bound to a specific HLA allele, in this case

HLA-A*32 and HLA-B*44, both Bw4 alleles. The differences probably arise both in the HLA alleles and in the subtypes of KIR receptors depending on the ethnic group studied. In the last decade, numerous studies have examined the importance of killer immunoglobulin-like receptors (KIR) on natural killer (NK) cells and their HLA class I ligands. The regulation of activity on these cells is under the control of a range of activating and inhibitory receptors that work in concert to identify and destroy aberrant target cells. Inhibitory receptors

have long cytoplasmic tails comprising immune-receptor tyrosine-based inhibitory motifs that translate inhibitory signals whereas the activating KIR do not have signalling find more motifs, but can associate with an adaptor through a positively charged residue in their transmembrane region. The adaptor molecules have immune-receptor tyrosine-based activation motifs that translate an activating signal when the receptor binds to their respective ligands.[1, 2] Several KIR and HLA interactions have been described. KIR and HLA loci are both highly polymorphic. The pairs of HLA class I ligands and the KIR that can be used to regulate the Tamoxifen in vitro NK cell responses vary between individuals within a population,

and are dependent upon the combination of KIR and HLA class I genes that each person inherits.[3-5] The activating NK cell receptor KIR3DS1 (KIR3 immunoglobulin-domain where ‘S’ stands for short cytoplasmic tail and ‘1’ is the particular gene) and the inhibitory receptor KIR3DL1 (KIR3 immunoglobulin-domain where ‘S’ stands for long cytoplasmic tail and ‘1’ is the particular gene) segregate as alleles of the same locus and share about 97% sequence similarity in their extracellular domain, suggesting that they may Anidulafungin (LY303366) bind similar ligands.[5, 6] The KIR3DL1 receptor binds the HLA-Bw4-80I allotypes with higher affinity.[6] Carr et al.[7] showed that KIR3DS1 receptors do recognize HLA-Bw4 ligands, this may be peptide dependent and although there is no direct evidence, genetic epidemiological data strongly support such an interaction. Bw4 epitopes of the HLA-B comprise B*13, B*27, B*37, B*38, B*44, B*47, B*49, B*51, B*52, B*53, B*57, B*58, B*59, B*1513 alleles and HLA-A comprise A*24, A*23, A*25, A*32;[6-8] see also the website http://hla.alleles.org/antigens. KIR3DS1 showed strong inhibition of HIV-1 replication in target cells that expressed HLA-Bw4-80I compared with those that did not show KIR3DS1. The specific combination of both activating and inhibitory KIR3DS1/KIR3DL1 and HLA-Bw4 alleles has been associated with delayed progression to AIDS.[9-11] Morvan et al.

This might have direct implication for all those clinical conditions relying on T-cell detection for diagnosis and prognosis. Furthermore, the finding that IL-7 elicits the expansion of tumour-specific T cells, in the absence of exogenous Ag provision provides a suitable alternative for all those situations for which the Ag remains to be identified. In the model system adopted in

this study, IL-7-expanded CD4+ T cells were capable of supporting the development of protective anti-tumour immunity, while IL-2 cultured cells were not. To date, Lapatinib manufacturer the clinical efficacy of ACT, although proven in recent clinical trails 1, remains limited to a fraction of the patients. This might be due to limitations imposed by current strategies Gefitinib clinical trial used to isolate tumour-specific lymphocytes,

and insufficient CD4+ T-cell help. Indeed, present ACT strategies mostly exploit Ag in combination with IL-2-driven T-cell stimulation, which favor production of effector CD8+ T cells lacking long-term survival 36, 50. In agreement, we found that IL-2, although capable of sustaining the proliferation/accumulation of in vivo Ag-sensitized CD4+ T cells without the need of exogenous Ag provision, did not promote viability/survival and LN homing to similar extents as IL-7. Alongside with effector cytokine production (IL-2 and IFN-γ secretion), IL-7-cultured CD4+ T cells maintained a less differentiated phenotype than IL-2 cultured CD4+ T cells, allowing superior persistence and LN homing when infused in tumour-bearing hosts. We found that replenishing the cultures with IL-7 after 7 days further promoted the accumulation of tumour-specific T cells (data not shown). At present it remains to be determined whether longer cultures will also preserve the poorly differentiated state of the cells, which might be critical for the in vivo efficacy. Most recently, IL-7 was also shown to promote the ex vivo expansion of CD8+ T cells 51, 52. This together with the notion that less differentiated T-cell subsets might be more potent than fully differentiated effector cells 53, suggest that

IL-7 should be preferred Urease to IL-2 when attempting the ex vivo expansion of CD4+ and CD8+ T cells to be used in anti-tumour ACT. TS/A-LACK cells do not express MHC class II molecules, and their parental cell line TS/A relies on CD8+ T cells to be rejected 47. We speculate that IL-7-expanded cells following ACT by migrating to T-dLN and to the tumour might provide help to CD8+ T cells and other immune effectors and by that favor tumour rejection. Thus, together with the finding that IL-7 and IL-15 drives the in vitro generation of self-renewing central memory human T lymphocytes 54, our data support the use of IL-7 for the identification and the expansion of clinically relevant T-cell subsets. Eight-week-old BALB/c mice were purchased from Charles River (Charles River Italia, Milan, Italy). 16.

Methods:  Lipopolysaccharide (LPS)-treated mice were used as an animal model of albuminuria. We evaluated the effect of HGF on slit proteins using immunohistochemistry, western blotting and real-time polymerase chain reaction. Results: 

Albuminuria occurred 36 h after LPS treatment in mice. This albuminuria did not involve podocyte loss, but was associated with a decrease in nephrin and its key anchor, synaptopodin. In these processes, c-Met tyrosine phosphorylation, which represented HGF signal activation, occurred in glomerular cells including podocytes. When recombinant HGF was administrated to nephritic mice, c-Met tyrosine phosphorylation became screening assay evident in podocytes. The enhancement of the HGF-c-Met signal was associated with increases in nephrin and synaptopodin. An electron microscopic examination revealed that LPS induced the foot process effacement of podocytes, while HGF injections suppressed the foot process injury. Overall, albuminuria was attenuated in the LPS-treated mice after HGF administration. Conclusion:  HGF protects podocytes from a loss of nephrin, at least in part, through maintaining synaptopodin. As a result, HGF was shown to sustain foot process structure, and albuminuria was attenuated under inflammation. “
“Kidney disease develops to renal failure over a period of days, months or years, hence, clinical markers that indicate

the real-time renal pathophysiological conditions is important. Liver type fatty acid binding protein (L-FABP) is GPX6 a 14 kDa molecule predominantly expressed GS-1101 in vitro in human proximal tubules. Clinical studies demonstrate that urinary excretion of L-FABP derived from the proximal tubules is an excellent biomarker for predicting and monitoring deterioration of renal function or for early detection of kidney

disease. However, in order to clarify the pathophysiological roles or dynamics of renal L-FABP in diseased settings, in vivo experimental studies of kidney diseases are indispensable. Since L-FABP is not endogenously expressed in murine kidneys, a transgenic (Tg) mouse model with expression of the human L-FABP gene was established. This review article summarizes the findings on the pathophysiological roles and dynamics of renal human L-FABP in the recent experimental studies performed using this Tg mouse model. The progression of kidney disease leads to renal failure, which requires renal replacement therapy with poor outcomes and at a high cost. Moreover, kidney disease is associated with the development and progression of cardiovascular1 or cerebrovascular disease.2 Therefore, clinical markers that accurately reflect the pathophysiological conditions of kidney disease are important in order to administer appropriate treatments and suppress the progression of kidney disease. Renal tubulointerstitial injury has been noted to have an important impact on the progression of kidney disease.