38 In that study, CS exposure was associated with increased ALT. Future studies are needed to better elucidate the mechanistic aspects of the effects of CS in NAFLD and to better characterize the JQ1 role of CS in human NAFLD. Nonetheless, this study provides one more reminder that there is already ample experimental

and clinical evidence consistently pointing in the same direction: CS aggravates liver injury in CLD. It is time to take the harmful effects of CS in CLD more seriously. As hepatologists, we need to incorporate the intake of a more thorough smoking history during our evaluations, educate our patients on the effects of this modifiable risk factor on liver injury, and strongly recommend smoking cessation check details in all patients with CLD. “
“Dominant negative form of transforming growth factor beta receptor type II (dnTGFβRII) mice, expressing a dominant negative form of TGFβ receptor II under control of the CD4 promoter, develop autoimmune colitis and cholangitis. Deficiency in interleukin (IL)-12p40

lead to a marked diminution of inflammation in both the colon and the liver. To distinguish whether IL-12p40 mediates protection by the IL-12 or IL-23 pathways, we generated an IL-23p19−/− dnTGFβRII strain deficient in IL-23, but not in IL-12; mice were longitudinally followed for changes in the natural history of disease and immune responses. Interestingly, IL-23p19−/− mice demonstrate dramatic improvement in their colitis, but no changes in biliary pathology; mice also manifest reduced T-helper (Th)17 cell populations and unchanged IFN-γ levels. We submit that the IL-12/Th1 pathway is essential for biliary disease pathogenesis, whereas the IL-23/Th17 pathway mediates colitis. To further assess the mechanism

of the IL-23-mediated protection from colitis, we generated an IL-17A−/− dnTGFβRII strain deficient in IL-17, a major effector cytokine produced by IL-23-dependent Th17 cells. Deletion of the IL-17A gene did not affect the severity of either cholangitis or colitis, suggesting click here that the IL-23/Th17 pathway contributes to colon disease in an IL-17-independent manner. These results affirm that the IL-12/Th1 pathway is critical to biliary pathology in dnTGFβRII mice, whereas colitis is caused by a direct effect of IL-23. (HEPATOLOGY 2012) Murine strains with a deficiency in specific cytokine pathways are important tools for investigating the mechanism of immunopathogenesis of autoimmunity. Mice transgenic for directed expression of a dominant negative form of transforming growth factor beta receptor type II (dnTGFβRII), under the control of the CD4 promoter lacking the CD8 silencer, spontaneously develop an inflammatory bowel disease (IBD).

38 In that study, CS exposure was associated with increased ALT. Future studies are needed to better elucidate the mechanistic aspects of the effects of CS in NAFLD and to better characterize the MK-8669 supplier role of CS in human NAFLD. Nonetheless, this study provides one more reminder that there is already ample experimental

and clinical evidence consistently pointing in the same direction: CS aggravates liver injury in CLD. It is time to take the harmful effects of CS in CLD more seriously. As hepatologists, we need to incorporate the intake of a more thorough smoking history during our evaluations, educate our patients on the effects of this modifiable risk factor on liver injury, and strongly recommend smoking cessation Seliciclib price in all patients with CLD. “
“Dominant negative form of transforming growth factor beta receptor type II (dnTGFβRII) mice, expressing a dominant negative form of TGFβ receptor II under control of the CD4 promoter, develop autoimmune colitis and cholangitis. Deficiency in interleukin (IL)-12p40

lead to a marked diminution of inflammation in both the colon and the liver. To distinguish whether IL-12p40 mediates protection by the IL-12 or IL-23 pathways, we generated an IL-23p19−/− dnTGFβRII strain deficient in IL-23, but not in IL-12; mice were longitudinally followed for changes in the natural history of disease and immune responses. Interestingly, IL-23p19−/− mice demonstrate dramatic improvement in their colitis, but no changes in biliary pathology; mice also manifest reduced T-helper (Th)17 cell populations and unchanged IFN-γ levels. We submit that the IL-12/Th1 pathway is essential for biliary disease pathogenesis, whereas the IL-23/Th17 pathway mediates colitis. To further assess the mechanism

of the IL-23-mediated protection from colitis, we generated an IL-17A−/− dnTGFβRII strain deficient in IL-17, a major effector cytokine produced by IL-23-dependent Th17 cells. Deletion of the IL-17A gene did not affect the severity of either cholangitis or colitis, suggesting learn more that the IL-23/Th17 pathway contributes to colon disease in an IL-17-independent manner. These results affirm that the IL-12/Th1 pathway is critical to biliary pathology in dnTGFβRII mice, whereas colitis is caused by a direct effect of IL-23. (HEPATOLOGY 2012) Murine strains with a deficiency in specific cytokine pathways are important tools for investigating the mechanism of immunopathogenesis of autoimmunity. Mice transgenic for directed expression of a dominant negative form of transforming growth factor beta receptor type II (dnTGFβRII), under the control of the CD4 promoter lacking the CD8 silencer, spontaneously develop an inflammatory bowel disease (IBD).

Pietrasiak for isolating this website and initial characterization of the strain UTEX B2979. “
“Teacher in the Computer Science Department, Shu-Te Home Economics and Commercial High School, Kaohsiung, Taiwan Postdoctoral Fellow in the Department of Agricultural Chemistry, National Taiwan University, Taipei, Taiwan Joint Doctoral Program in Marine Biotechnology between National Sun Yat-sen University and Academia Sinica, Taiwan Full-length protein disulfide isomerase (UfPDI) cDNA was cloned from the intertidal macroalga Ulva lactuca Linnaeus. Modulation of UfPDI expression by stresses and polyamines

(PA) was studied. UfPDI transcription and enzyme activity were increased by hypersalinity (90) or high light illumination (1,200 μmol photons · m−2 · s−1), decreased by the addition of 100 μM CuSO4. An exposure to a salinity of 90 decreased PA contents. Treating with PA biosynthetic inhibitors, D-arginine (D-Arg) or α-methyl ornithine (α-MO), led to a further decrease and also inhibited UfPDI expression and recovery of the growth rate. These results suggest that PAs are required

to activate Selleckchem Ulixertinib UfPDI expression with hypersalinity, even PA contents are decreased at a salinity of 90. The induction of UfPDI expression by hypersalinity of 90 and tolerance to hypersalinity could be enhanced if internal PA contents rise. Sung et al. (2011b) showed that PA contents could be increased by pretreating with putrescine (Put, 1 mM), spermidine (Spd, 1 mM), or spermine (Spm, 1 mM) at a salinity of 30. Therefore, PA pretreatment effect on UfPDI expression was examined. Pretreatment with Spd and Spm, but not with Put, enhanced UfPDI expression after transferred to a salinity of 90 and restored the growth rate. In conclusion, induction of UfPDI expression by Spd or Spm before exposure to hypersaline conditions and continuous up-regulation after hypersalinity exposure are required for the acquisition of hypersalinity tolerance in the intertidal green macroalga U. lactuca.

“
“The cnidarian-dinoflagellate mutualism is click here integral to the survival of the coral-reef ecosystem. Despite the enormous ecological and economic importance of corals, their cellular and molecular biology and the ways in which they respond to environmental change are still poorly understood. We have been developing a proxy system for examining the coral mutualism in which the dinoflagellate symbiont Symbiodinium is introduced into a clonal population of the host Aiptasia, a small sea anemone closely related to corals. To further develop the tools for this system, we generated five clonal, axenic strains of Symbiodinium and verified the lack of contaminants by growth on rich medium, microscopic examination, and PCR analysis. These strains were assigned to clades A (two strains), B, E, and F based on their chloroplast 23S rDNA sequences.

Pietrasiak for isolating buy FDA-approved Drug Library and initial characterization of the strain UTEX B2979. “
“Teacher in the Computer Science Department, Shu-Te Home Economics and Commercial High School, Kaohsiung, Taiwan Postdoctoral Fellow in the Department of Agricultural Chemistry, National Taiwan University, Taipei, Taiwan Joint Doctoral Program in Marine Biotechnology between National Sun Yat-sen University and Academia Sinica, Taiwan Full-length protein disulfide isomerase (UfPDI) cDNA was cloned from the intertidal macroalga Ulva lactuca Linnaeus. Modulation of UfPDI expression by stresses and polyamines

(PA) was studied. UfPDI transcription and enzyme activity were increased by hypersalinity (90) or high light illumination (1,200 μmol photons · m−2 · s−1), decreased by the addition of 100 μM CuSO4. An exposure to a salinity of 90 decreased PA contents. Treating with PA biosynthetic inhibitors, D-arginine (D-Arg) or α-methyl ornithine (α-MO), led to a further decrease and also inhibited UfPDI expression and recovery of the growth rate. These results suggest that PAs are required

to activate MK-1775 cost UfPDI expression with hypersalinity, even PA contents are decreased at a salinity of 90. The induction of UfPDI expression by hypersalinity of 90 and tolerance to hypersalinity could be enhanced if internal PA contents rise. Sung et al. (2011b) showed that PA contents could be increased by pretreating with putrescine (Put, 1 mM), spermidine (Spd, 1 mM), or spermine (Spm, 1 mM) at a salinity of 30. Therefore, PA pretreatment effect on UfPDI expression was examined. Pretreatment with Spd and Spm, but not with Put, enhanced UfPDI expression after transferred to a salinity of 90 and restored the growth rate. In conclusion, induction of UfPDI expression by Spd or Spm before exposure to hypersaline conditions and continuous up-regulation after hypersalinity exposure are required for the acquisition of hypersalinity tolerance in the intertidal green macroalga U. lactuca.

“
“The cnidarian-dinoflagellate mutualism is selleck chemicals integral to the survival of the coral-reef ecosystem. Despite the enormous ecological and economic importance of corals, their cellular and molecular biology and the ways in which they respond to environmental change are still poorly understood. We have been developing a proxy system for examining the coral mutualism in which the dinoflagellate symbiont Symbiodinium is introduced into a clonal population of the host Aiptasia, a small sea anemone closely related to corals. To further develop the tools for this system, we generated five clonal, axenic strains of Symbiodinium and verified the lack of contaminants by growth on rich medium, microscopic examination, and PCR analysis. These strains were assigned to clades A (two strains), B, E, and F based on their chloroplast 23S rDNA sequences.

For negative control, the primary antibody was omitted in the protocol. Slides were viewed under an Axioskop 40 (Zeiss) upright

research microscope and digital images obtained. Collages were prepared using Adobe Photoshop CS3 software (San Jose, CA). For quantification of proliferating cell nuclear antigen (PCNA)-positive cells, five high-power field images were taken for each animal and counted utilizing Zeiss Axiovision software. For measurement of fibrosis, Masson’s trichrome staining was performed. Photomicrographs were taken at 50× magnification and percentage of the area of fibrosis measured using Adobe Photoshop as described.10 Please refer to the online supplement for details on methods for this section. Please refer to the online supplement for details on methods for this section. All experiments were performed three or more times or with three or more animals and representative data check details are presented. Quantification of positive cells (A6, PCNA), serum biochemistry measurements, and fibrosis measurements were compared for statistical analysis by Student’s t test (Excel) and P less than 0.05 was considered significant. We previously reported a blunted atypical ductular proliferation in β-catenin KO after DDC feeding for 2 and 3.5 weeks.6 To further examine the impact of β-catenin loss on chronic hepatic injury, we placed KO and WT mice on a long-term DDC diet for time periods ranging from 30 to 150 days. H&E staining,

MAPK inhibitor along with immunofluorescence, was on liver samples from these timepoints. Interestingly, H&E staining showed a clear increase in atypical ductular reaction in the KO liver when compared to WT at 80 and 150 days of DDC feeding (Fig. 1A). To verify and quantify, atypical ductular response, immunofluorescence for A6, a marker that recognizes atypical ductules and oval cells, was performed. Indeed, significantly more A6-positive selleck inhibitor cells are found in the KO liver at 80 and 150 days of DDC feeding (Fig. 1B,C). We also observed an increase in PCNA-positive ductular cells

in the KO livers at 30, 80, and 150 days of DDC feeding when compared to the WT (shown 30 and 150 days, Fig. 1D,E). CD45-positive inflammatory cells were comparably present in KO and WT livers at all stages (data not shown). These findings suggest that a greater atypical ductular reaction due to enhanced proliferation occurs after an initial delay in the KO mice after chronic DDC injury. To monitor hepatic injury after long-term DDC feeding, serum analysis was performed for AST, ALT, bilirubin, and ALP. Levels of AST were modestly higher at 150 days of DDC feeding in WT compared to KO, whereas ALT levels were higher in WT at 80 and 150 days (Table 1). This finding was surprising, given that we expected KO to be more susceptible to hepatocyte injury. Conversely, serum bilirubin levels were significantly higher in the KO at 80 days with a trend toward being higher in KO at 150 days. Additionally, levels of ALP were higher in KO at 150 days of DDC feeding.

5; 95% CI 1.7-42.3). The headache selleck products after treatment was not associated with the risk of anxiety or depression after the intervention. Patients who underwent craniotomy had an increased risk of headache after treatment of intracranial aneurysms. The incidence of persistent headache after 3 months was higher

among patients who had anxiety before the intervention. “
“To report a migraineur with osmophobia and trigger to garlic and onion aroma. While odors serve as a trigger in 70% of migraineurs, alliaceous aromas have been described only rarely. Furthermore, nor has more than one type of alliaceous odor acted as a trigger in the same individual. Neither has migraine with aura been described as precipitated by such aromas. A patient experiencing migraines with aura, triggered almost exclusively by alliaceous aromas, is described. Case study: 32-year-old woman; 5 years previously felt nasal HIF inhibitor pruritis upon eating a red onion dip. Shortly thereafter, the mere aroma of raw onions caused a sensation of her throat closing along with an associated

panic attack. Over the intervening years, upon exposure to onions and garlic aroma she experienced a fortification spectra and visual entopia, followed by a bipareital, crushing level 10/10 headache, burning eyes and nose, lacrimation, perioral paresthesias, generalized pruritis, nausea, fatigue, sore throat, dysarthria, confusion, find more dyspnea, palpitations, presyncopal sensations, hand spasms, tongue soreness, neck pain, phonophobia, and photophobia. These would persist for 1 hour after leaving the aroma. She was unresponsive to medication and would wear a surgical mask when out. The patient also experienced chemosensory complaints: dysosmias every few months; phantosmias of food or cleaning products every month for a minute of level 5/10 intensity; pallinosmia of onion or garlic odor for 30 minutes after exposure; and metallic pallinugeusia after eating with

metal utensils. Neurological exam normal except for bilateral positive Hoffman reflexes. Quick Smell Identification Test 3/3 and Brief Smell Identification Test 12/12 were normal. Magnetic resonance imaging and computed tomography with and without contrast normal. Allergy skin test was positive for garlic and onion. Nose plug and counter stimulation with peppermint prevented the onset of headaches and associated symptoms. This is the first report of migraines with aura triggered by more than one alliaceous compound in the same individual. Possible mechanisms include odor induced, emotional change, vasomotor instability, trigeminal-induced neurogenic inflammation, and allergic response. In alliaceous and odor-induced migraines, a trial of counter stimulation and nose plugs is warranted. “
“(Headache 2011;51:804-818) The typical symptom of intracranial hypotension syndrome is orthostatic headache.

5; 95% CI 1.7-42.3). The headache Sotrastaurin after treatment was not associated with the risk of anxiety or depression after the intervention. Patients who underwent craniotomy had an increased risk of headache after treatment of intracranial aneurysms. The incidence of persistent headache after 3 months was higher

among patients who had anxiety before the intervention. “
“To report a migraineur with osmophobia and trigger to garlic and onion aroma. While odors serve as a trigger in 70% of migraineurs, alliaceous aromas have been described only rarely. Furthermore, nor has more than one type of alliaceous odor acted as a trigger in the same individual. Neither has migraine with aura been described as precipitated by such aromas. A patient experiencing migraines with aura, triggered almost exclusively by alliaceous aromas, is described. Case study: 32-year-old woman; 5 years previously felt nasal Alectinib chemical structure pruritis upon eating a red onion dip. Shortly thereafter, the mere aroma of raw onions caused a sensation of her throat closing along with an associated

panic attack. Over the intervening years, upon exposure to onions and garlic aroma she experienced a fortification spectra and visual entopia, followed by a bipareital, crushing level 10/10 headache, burning eyes and nose, lacrimation, perioral paresthesias, generalized pruritis, nausea, fatigue, sore throat, dysarthria, confusion, this website dyspnea, palpitations, presyncopal sensations, hand spasms, tongue soreness, neck pain, phonophobia, and photophobia. These would persist for 1 hour after leaving the aroma. She was unresponsive to medication and would wear a surgical mask when out. The patient also experienced chemosensory complaints: dysosmias every few months; phantosmias of food or cleaning products every month for a minute of level 5/10 intensity; pallinosmia of onion or garlic odor for 30 minutes after exposure; and metallic pallinugeusia after eating with

metal utensils. Neurological exam normal except for bilateral positive Hoffman reflexes. Quick Smell Identification Test 3/3 and Brief Smell Identification Test 12/12 were normal. Magnetic resonance imaging and computed tomography with and without contrast normal. Allergy skin test was positive for garlic and onion. Nose plug and counter stimulation with peppermint prevented the onset of headaches and associated symptoms. This is the first report of migraines with aura triggered by more than one alliaceous compound in the same individual. Possible mechanisms include odor induced, emotional change, vasomotor instability, trigeminal-induced neurogenic inflammation, and allergic response. In alliaceous and odor-induced migraines, a trial of counter stimulation and nose plugs is warranted. “
“(Headache 2011;51:804-818) The typical symptom of intracranial hypotension syndrome is orthostatic headache.

In the liver, NK cells express higher basal levels of TRAIL and have higher cytotoxic activity than peripheral NK cells. Additionally, TRAIL expression on liver NK cells is up-regulated by a range of factors (such as IFN-α, IFN-γ, TLR3 ligand, and so forth) and contributes to this website liver NK cell killing of activated stellate cells, stressed hepatocytes, and biliary epithelial cells in animal models of liver injury and in patients with liver disease.8 Interestingly, Shimoda et al.7 also confirmed that IFN-α treatment up-regulated TRAIL expression in liver NK cells and that TRAIL was a major factor

contributing to the cytotoxicity of NK cells against autologous biliary epithelial cells. Another interesting finding

from this publication was that the TLR4 ligand, lipopolysaccharide (LPS), in synergy with IFN-α, was able to activate NK cells, which may have significant implications on the pathogenesis of other liver diseases. It is well known that gut bacteria–derived LPS is central to the pathogenesis of various types of liver disorders, including steatohepatitis,20, 21 fibrosis,22, 23 and liver cancer.24 Early Selinexor manufacturer studies suggested that LPS activation of TLR4 on Kupffer cells plays a central role in pathogenesis of these liver disorders.25 Recent studies report that LPS also activates TLR4 on hepatic stellate cells,22 sinusoidal endothelial cells,23 and hepatocytes,26 contributing to fibrogenesis and hepatocellular damage. The study by Shimoda et al.7 highlight an unappreciated mechanism by which LPS may contribute to the pathogenesis of liver diseases by activation of NK cells. Although Shimoda et al.7 reported that LPS alone did not induce the cytotoxicity of NK cells against autologous biliary epithelial cells, previous studies have shown that human NK cells express TLR4, and that LPS treatment stimulated human CD56+ NK cells to produce IFN-γ.27 This suggests that LPS alone is sufficient to stimulate NK cell production of cytokines, but is not able to enhance NK cell cytotoxicity. In addition, LPS can also stimulate macrophages,

dendritic cells, and mast cells to produce cytokines that activate NK cells indirectly. Because hepatic LPS levels are elevated selleck screening library in alcoholic liver disease,20 it would be interesting to examine whether elevated LPS can activate NK cells, thereby contributing to the pathogenesis of this disease. In summary, Shimoda et al.7 provided convincing in vitro evidence that NK cells kill autologous biliary epithelial cells, and that NK cells from patients with PBC have higher activity than those from patients with other liver diseases. However, the exact role of NK cells in the pathogenesis of PBC still remains unsolved. Figure 1 summarizes the potential roles of NK cell activation in the pathogenesis of PBC.

In the liver, NK cells express higher basal levels of TRAIL and have higher cytotoxic activity than peripheral NK cells. Additionally, TRAIL expression on liver NK cells is up-regulated by a range of factors (such as IFN-α, IFN-γ, TLR3 ligand, and so forth) and contributes to Small Molecule Compound Library liver NK cell killing of activated stellate cells, stressed hepatocytes, and biliary epithelial cells in animal models of liver injury and in patients with liver disease.8 Interestingly, Shimoda et al.7 also confirmed that IFN-α treatment up-regulated TRAIL expression in liver NK cells and that TRAIL was a major factor

contributing to the cytotoxicity of NK cells against autologous biliary epithelial cells. Another interesting finding

from this publication was that the TLR4 ligand, lipopolysaccharide (LPS), in synergy with IFN-α, was able to activate NK cells, which may have significant implications on the pathogenesis of other liver diseases. It is well known that gut bacteria–derived LPS is central to the pathogenesis of various types of liver disorders, including steatohepatitis,20, 21 fibrosis,22, 23 and liver cancer.24 Early see more studies suggested that LPS activation of TLR4 on Kupffer cells plays a central role in pathogenesis of these liver disorders.25 Recent studies report that LPS also activates TLR4 on hepatic stellate cells,22 sinusoidal endothelial cells,23 and hepatocytes,26 contributing to fibrogenesis and hepatocellular damage. The study by Shimoda et al.7 highlight an unappreciated mechanism by which LPS may contribute to the pathogenesis of liver diseases by activation of NK cells. Although Shimoda et al.7 reported that LPS alone did not induce the cytotoxicity of NK cells against autologous biliary epithelial cells, previous studies have shown that human NK cells express TLR4, and that LPS treatment stimulated human CD56+ NK cells to produce IFN-γ.27 This suggests that LPS alone is sufficient to stimulate NK cell production of cytokines, but is not able to enhance NK cell cytotoxicity. In addition, LPS can also stimulate macrophages,

dendritic cells, and mast cells to produce cytokines that activate NK cells indirectly. Because hepatic LPS levels are elevated selleck screening library in alcoholic liver disease,20 it would be interesting to examine whether elevated LPS can activate NK cells, thereby contributing to the pathogenesis of this disease. In summary, Shimoda et al.7 provided convincing in vitro evidence that NK cells kill autologous biliary epithelial cells, and that NK cells from patients with PBC have higher activity than those from patients with other liver diseases. However, the exact role of NK cells in the pathogenesis of PBC still remains unsolved. Figure 1 summarizes the potential roles of NK cell activation in the pathogenesis of PBC.

In the liver, NK cells express higher basal levels of TRAIL and have higher cytotoxic activity than peripheral NK cells. Additionally, TRAIL expression on liver NK cells is up-regulated by a range of factors (such as IFN-α, IFN-γ, TLR3 ligand, and so forth) and contributes to R428 purchase liver NK cell killing of activated stellate cells, stressed hepatocytes, and biliary epithelial cells in animal models of liver injury and in patients with liver disease.8 Interestingly, Shimoda et al.7 also confirmed that IFN-α treatment up-regulated TRAIL expression in liver NK cells and that TRAIL was a major factor

contributing to the cytotoxicity of NK cells against autologous biliary epithelial cells. Another interesting finding

from this publication was that the TLR4 ligand, lipopolysaccharide (LPS), in synergy with IFN-α, was able to activate NK cells, which may have significant implications on the pathogenesis of other liver diseases. It is well known that gut bacteria–derived LPS is central to the pathogenesis of various types of liver disorders, including steatohepatitis,20, 21 fibrosis,22, 23 and liver cancer.24 Early Y-27632 mouse studies suggested that LPS activation of TLR4 on Kupffer cells plays a central role in pathogenesis of these liver disorders.25 Recent studies report that LPS also activates TLR4 on hepatic stellate cells,22 sinusoidal endothelial cells,23 and hepatocytes,26 contributing to fibrogenesis and hepatocellular damage. The study by Shimoda et al.7 highlight an unappreciated mechanism by which LPS may contribute to the pathogenesis of liver diseases by activation of NK cells. Although Shimoda et al.7 reported that LPS alone did not induce the cytotoxicity of NK cells against autologous biliary epithelial cells, previous studies have shown that human NK cells express TLR4, and that LPS treatment stimulated human CD56+ NK cells to produce IFN-γ.27 This suggests that LPS alone is sufficient to stimulate NK cell production of cytokines, but is not able to enhance NK cell cytotoxicity. In addition, LPS can also stimulate macrophages,

dendritic cells, and mast cells to produce cytokines that activate NK cells indirectly. Because hepatic LPS levels are elevated selleck chemicals llc in alcoholic liver disease,20 it would be interesting to examine whether elevated LPS can activate NK cells, thereby contributing to the pathogenesis of this disease. In summary, Shimoda et al.7 provided convincing in vitro evidence that NK cells kill autologous biliary epithelial cells, and that NK cells from patients with PBC have higher activity than those from patients with other liver diseases. However, the exact role of NK cells in the pathogenesis of PBC still remains unsolved. Figure 1 summarizes the potential roles of NK cell activation in the pathogenesis of PBC.