Biomedical subjects

Y K Kim

Publications and source records attributed to Y K Kim.

At least 127 records · Page 7Linked to original sources

PubMed2000

Association of HLA-DRB1()07 and DRB1()04 to citrus red mite (Panonychus citri) and house dust mite sensitive asthma.

BACKGROUND: Specific IgE responses to allergens provide useful models for evaluating the genetic factors that control human immune responses. A recent survey demonstrated that the citrus red mite (Panonychus citri, CRM) is the most important allergen in the development of asthma in citrus farmers. OBJECTIVE: The aim of this study was to evaluate whether susceptibility or resistance to CRM-induced asthma was associated with HLA-DRB1 gene. METHODS: DNAs were extracted from two groups of unrelated Korean adults living around citrus farms: (1) Ninety-one adults with CRM-sensitive asthma; and (2) 98 exposed, healthy nonatopic controls. Genotypes of HLA-DRB1 alleles were carried out using PCR-based methods. RESULTS: Allelic frequency of HLA-DRB1(*)07 was higher in the CRM-sensitive asthmatics compared to the controls (17.6% vs 4.1%, Pc = 0.01). Conversely, the frequency of DRB1*04 was lower in the CRM-sensitive asthmatics compared to the controls (19.8% vs 40.8%, Pc = 0.01). No significant difference was found in the distributions of the other HLA-DRB1 gene-encoded antigens between the two groups. CONCLUSION: HLA-DRB1 genes may be involved in the development of CRM-induced asthma. In addition, HLA-DR7 may increase, and DR4 decrease, the risk of developing the asthma in CRM-exposed adults.

Adult↗

PubMed2000

Solution structure of the antimicrobial peptide gaegurin 4 by H and 15N nuclear magnetic resonance spectroscopy.

Gaegurin 4 (GGN4) is a 37-residue antimicrobial peptide isolated from the skin of a Korean frog, Rana rugosa. This peptide shows a broad range of activity against prokaryotic cells but shows very little hemolytic activity against human red blood cells. The solution structure of GGN4 was studied by using circular dichroism (CD) and NMR spectroscopy. CD investigations revealed that GGN4 adopts mainly an alpha-helical conformation in trifluoroethanol/water solution, in dodecylphosphocholine and in SDS micelles, but adopts random structure in aqueous solution. By using both homonuclear and heteronuclear NMR experiments, complete 1H and 15N resonance assignments were obtained for GGN4 in 50% trifluoroethanol/water solution. The calculated structures of GGN4 consist of two amphipathic alpha-helices extending from residues 2-10 and from residues 16-32. These two helices are connected by a flexible loop spanning between the residues 11 and 15. By using enzyme digestion and matrix-assisted laser desorption/ionization mass spectroscopy, we confirmed that GGN4 contains a disulfide bridge formed between the residues Cys31 and Cys37 in its C-terminus. The effect of disulfide bridge on the structure and the activity of GGN4 was investigated. The reduced form of GGN4 revealed a similar activity and conformation to native GGN4, suggesting that the disulfide bridge does not strongly affect the conformation and the antimicrobial activity of GGN4.

Amino Acid Sequence↗

PubMed2000

Incidence and prevalence of ulcerative colitis in the Songpa-Kangdong District, Seoul, Korea, 1986-1997.

BACKGROUND AND AIMS: Ulcerative colitis (UC) is regarded as a rare disease in developing countries, but accurate data are generally lacking. We performed the present study to evaluate the incidence and prevalence of UC in Korea. METHODS: A retrospective study was performed from 1986 to 1997 in the Songpa-Kangdong district of Seoul, Korea. To recruit UC patients as completely as possible, multiple information sources including all medical facilities in the study area and three referral centres located nearby, but outside the study area were used. The incidence and prevalence rates were adjusted using the 1997 Korean population statistics. RESULTS: During the study period, a total of 94 incident cases were identified, for an adjusted mean annual incidence rate of 0.68 per 100,000 inhabitants. On 31 December 1997, 91 patients with UC lived in the study area, giving an adjusted prevalence rate of 7.57 per 100,000 inhabitants. By using the Poisson regression analysis, the annual incidence rate increased significantly from 0.20 per 100,000 inhabitants in 1986-1988 to 1.23 per 100,000 inhabitants in 1995-1997 (P < 0.005). Patient age at diagnosis, the interval from onset of symptoms to diagnosis, and the disease extent at diagnosis were fairly constant throughout the study period. CONCLUSIONS: The incidence and prevalence of UC in our study area are still low compared with those of Western countries, but the incidence rate is steadily increasing.

Adult↗

PubMed2000

Cytotoxic triterpenes from stem bark of Physocarpus intermedius.

Seven triterpenes (1-7), i.e., betulinic acid 1, ursolic acid 2, oleanolic acid 3, 3-O-caffeoyloleanolic acid 4, euscaphic acid 5, 2 alpha-hydroxyursolic acid 6 and maslinic acid 7 were isolated from the stem bark extract of P. intermedius as active principles responsible for the cytotoxicity against five cultured human tumor cell lines, i.e., A549 (non small cell lung), SK-OV-3 (ovary), SK-MEL-2 (melanoma), XF498 (central nerve system) and HCT-15 (colon), in vitro.

Antineoplastic Agents, Phytogenic↗

PubMed2000

Determination of ethyl carbamate in some fermented Korean foods and beverages.

Ethyl carbamate has been associated with cancer for several decades. It is mainly found in fermented foods and beverages. In view of the importance of fermented foods in the Korean diet and the significant level of ethyl carbamate expected, we determined ethyl carbamate concentrations in some of the staple food items and estimated the daily intake for the Korean population. Ethyl carbamate in commercial samples of kimchi, soy sauce, vinegar, soybean paste, and alcoholic beverages were determined by gas chromatography-mass spectrometry/selective ion monitoring (GC-MS/SIM). Homemade soy sauce and kimchi were also analysed. The maximum ethyl carbamate concentrations observed were 73 micrograms/kg in soy sauce, 7.9 micrograms/kg in soybean paste, 2.5 micrograms/l in vinegar, 16.2 micrograms/kg in kimchi and 15.4 mu/l in Korean traditional alcoholic beverages. Combining these values with the average daily food intake data, we estimated that the maximum daily exposure of Korean population to ethyl carbamate is 2.8 micrograms/day, which is not a negligible amount considering the 'virtually safe dose' derived by animal experiment ranges between 1.2 and 4.8 micrograms/day. It would be desirable to closely monitor ethyl carbamate levels in Korean foods and to find ways to reduce the daily intake.

Alcoholic Beverages↗

PubMed2000

Prevalence and patterns of nocturnal bruxofacets on stabilization splints in temporomandibular disorder patients.

The purpose of this study was to investigate the prevalence of nocturnal bruxism, the characteristics of bruxofacets, and the reduction of symptoms in temporomandibular disorder (TMD) patients. The study involved the observation of bruxofacets on a stabilization splint. Twenty-six patients (22 women and 4 men, 16-54 years of age) with signs and symptoms of TMD were given an initial examination before using a splint, and then at intervals of one, three, six and ten weeks after a stabilization splint was first used. In 88% of the patients (n = 23) active shiny facets or scratches caused by nocturnal bruxism appeared on the occlusal surface of splints within ten weeks. In 52% of the 23 patients these facets were created by bilateral mandibular excursions, in 35% by small lateral movements, and in 13% by unilateral excursions. Subjective pain and the Craniomandibular Index in patients had decreased after ten weeks (p < 0.001), but a reduction of symptoms did not differ according to the patterns of the bruxofacets. It was concluded that most TMD patients have a parafunctional habit, namely bruxism. Further research is needed to produce more convincing evidence of a true cause-and-effect relationship between nocturnal bruxism and TMD.

Adolescent↗

PubMed2000

Mechanism of reduced GFR in rabbits with ischemic acute renal failure.

A reduction in glomerular filtration rate (GFR) is a primary characteristic of ischemic acute renal failure. The present study was undertaken to examine the roles of angiotensin II, tubuloglomerular-feedback (TGF) mechanism, and tubular obstruction for the GFR reduction in the post-ischemic kidney. Renal ischemia was induced by occlusion of the bilateral renal arteries for 60 min, and renal function was examined at 2 and 24 h after the onset of reflow. After the end of 2-h reflow, the GFR was not significantly changed, but the urine flow increased significantly. On the other hand, at the end of 24-h reflow, the GFR and urine flow decreased markedly along with increased filtration fraction. The renal blood flow significantly decreased at 24 h, but not 2 h, after reflow, which was accompanied by increased total renal vascular resistance. Furosemide infusion (1 mg/min/kg) after 24 h of reflow prevented the reduction in GFR and filtration fraction without no changes in renal blood flow and total renal vascular resistance. Pretreatment of enalapril and losartan did not prevent the reduction in GFR, indicating that angiotensin II was not involved. In morphological examinations, tubular obstruction was seen in the proximal and distal tubules of kidneys both at 2 and 24 h after the onset of reflow. In two rabbits subjected to 48 h of reflow, the tubular obstruction was not observed, despite GFR remained depressed. These results suggest that the late reduction in GFR in postischemic kidneys is not mediated by angiotensin II, but is mediated, at least in part, by the TGF mechanism. The tubular obstruction may be not prerequisite for the GFR reduction in rabbits.

Acute Kidney Injury↗

PubMed2000

Effect of arachidonic acid metabolic inhibitors on hypoxia/reoxygenation-induced renal cell injury.

The present study was undertaken to examine the role of arachidonic acid (AA) metabolites in hypoxia/reoxygenation (H/R)-induced renal cell injury in rabbit renal cortical slices using AA metabolic inhibitors. Inhibitors of cyclooxygenase (indomethacin and diclofenac sodium) and lipoxygenase pathways (nordihydroguaiaretic acid, caffeic acid, and eicosapentaenoic acid) reduced H/R-induced LDH release in a dose-dependent manner, whereas an inhibitor of cytochrome P-450 monooxygenase pathway ethoxyresorufin was not effective. AA increased LDH release in control slices, and the effect was not altered by indomethacin and nordihydroguaiaretic acid. The protective effect of indomethacin was not affected by addition of PGE2, a main product of cyclooxygenase pathway in the kidney. H2O2-induced LDH release was prevented by inhibitors of lipoxygenase but not by inhibitors of cyclooxygenase and cytochrome P-450 monooxygenase H/R-induced LDH release was not altered by iron chelators, phenanthroline and deferoxamine, and a potent antioxidant, N,N'-diphenyl-p-phenylenediamine, suggesting that the H/R-induced cell injury is not attributed to a generation of reactive oxygen species. Morphological studies showed that H/R-induced structural changes including cell necrosis were significantly prevented by indomethacin. These results suggest that inhibitors of cyclooxygenase and lipoxygenase pathways exert a direct protective effect against the H/R-induced cell injury in renal tubules. Whether these effects are mediated by alterations of AA metabolic pathways is not certain.

Animals↗

PubMed2000

Changes in expression of sodium cotransporters and aquaporin-2 during ischemia-reperfusion injury in rabbit kidney.

Ischemic renal injury is associated with defects in transport functions of the proximal tubules and urinary concentration ability. To determine whether alterations in expression of various transporter genes contribute to an impairment in renal functions, the expression of various solute transport genes was analyzed in renal cortex and medulla of rabbits with ischemic acute renal failure. Rabbits were subjected to 60 min of renal pedicle clamping followed by 24, 48, or 72 h of reperfusion. Urine volume and glomerular filtration rate were markedly decreased, which were accompanied by an increase in serum creatinine level and fraction Na+ excretion. Glucosuria and phosphaturia were evident during reperfusion periods. These alterations in renal functions were persisted to 72 h after reperfusion. The Na+-dependent uptakes of glucose and phosphate by brush border membrane vesicles were inhibited by 24 h of reperfusion. mRNA levels for Na+-glucose, Na+-phosphate, and Na+-succinate cotransporter analyzed by RT-PCR were not changed by 60 min of ischemia alone, but were significantly reduced by 24 h of reperfusion. mRNA levels for apical Na+-K+-2Cl- cotransporter, NaCl cotransporter, and turea transporter in the medulla were not changed during reperfusion. Protein levels for AQP2 in the medulla, but not AQP1 in the cortex, analyzed by Western blot were significantly reduced at 24 h after reperfusion. These results suggest that reductions in expression of Na+-cotransporter genes in the proximal tubules may be important factors in the impairment in Na+-dependent reabsorption of solutes and that decrease in AQP2 protein may be involved in defect in urinary concentration ability in rabbits with ischemic acute renal failure.

Analysis of Variance↗

PubMed2000

Mouse monoclonal antibodies to hepatitis B virus preS1 produced after immunization with recombinant preS1 peptide.

We have efficiently generated mouse monoclonal antibodies (MAbs), which bind specifically to amino acids 21-47 of the preS1 domain of hepatitis B virus (HBV) by immunizing mice with the preS1 peptide (amino acids, aa 1-56) conjugated to keyhole limpet hemocyanin. Hybridomas were screened by an indirect enzyme-linked immunosorbent assay (ELISA) using the purified preS1 peptide as a coated antigen. Eighteen positive hybridomas were selected and subjected to isotyping. Of these, 5 clones secreted immunoglobulin G (IgG) and 13 clones secreted IgM. Four (KR1, KR2, KR3, and KR4) of the 5 IgG MAbs bound to preS1 peptide (aa 21-47). Epitope mapping using bacterially expressed GST fusion proteins revealed that three clones (KR2, KR3, KR4) (IgG1, K) recognize aa 21-35, while KR1 (IgG2a, K) recognizes aa 35-47 of the preS1. These MAbs immunoprecipitated HBV particles, demonstrating that they bind to native HBV particles.

Animals↗

PubMed2000

Perfluorocarbon blocks tumor necrosis factor-alpha-induced interleukin-8 release from alveolar epithelial cells in vitro.

OBJECTIVE: To determine whether tumor necrosis factor (TNF)-alpha-induced interleukin (IL)-8 production by pulmonary alveolar epithelial cells is blocked by perfluorocarbon (PFC). DESIGN: Controlled, laboratory investigation of IL-8 production by pulmonary alveolar epithelial cells after exposure to PFC in vitro. SETTING: University research laboratory. SUBJECT: The human alveolar epithelial cell line with pulmonary type II (A549) cell properties. INTERVENTIONS: The A549 cells on a polycarbonate porous filter were stimulated either on the apical or the basolateral side with TNF-alpha. To determine TNF-alpha-induced IL-8 production, IL-8 was measured by using a human IL-8 kit in both control and experimental groups. MEASUREMENTS AND MAIN RESULTS: TNF-alpha stimulation induced a large increase in IL-8. When PFC was added to the medium immediately after TNF-alpha stimulation, PFC separated the medium from the cells and IL-8 production was markedly reduced (TNF-alpha alone, 8342+/-470 pg vs. TNF-alpha followed by PFC, 417+/-88 pg, p < .05). Preincubation of A549 cells with PFC for 24 hrs before stimulation with TNF-alpha followed by removal of PFC did not affect IL-8 production (8834+/-204 vs. 8342+/-470 pg; p = NS). When added to the lower chamber, TNF-alpha also induced IL-8 production unaffected by the addition of PFC to the upper chamber. The decrease in TNF-alpha-induced IL-8 production depended on the time of PFC administration after the initiation of TNF-alpha stimulation. The earlier PFC was added, the more pronounced the diminution was in IL-8. CONCLUSIONS: PFC appears to function as a physical barrier, thus reducing cytokines produced by alveolar epithelial cells in vitro. This mechanism may partially explain the decreased inflammatory response observed during liquid ventilation in models of acute lung injury.

Adenocarcinoma, Bronchiolo-Alveolar↗

PubMed2000

A mitogen-activated protein kinase kinase required for induction of cytokinesis and appressorium formation by host signals in the conidia of Colletotrichum gloeosporioides.

Differentiation of fungal conidia of phytopathogens into the infection structure, appressorium, requires contact with a hard surface and host signals. The molecular signaling involved in the induction of this differentiation is poorly understood. We report the cloning of a mitogen-activated protein kinase kinase (MEK), CgMEK, from Colletotrichum gloeosporioides and its role in the induction of these developmental processes involved in pathogenesis. Disruption of CgMEK1 resulted in the loss of its ability to form appressoria in response to the host's signals and a loss of virulence. Results of confocal microscopic examination of germinating conidia of the gene-disrupted mutants were similar to those for wild-type conidia treated with an MEK inhibitor, suggesting that CgMEK1 is involved in two developmental processes in the differentiation into appressorium: (1) polarized cell division, with the preferential increase in F-actin in one of the daughter nuclei after nuclear division and the formation of septum; and (2) differentiation of the germ tube into an appressorium. CgMEK1 is required for the differentiation.

Actins↗

PubMed2000

Analysis of the polar flagellar gene system of Vibrio parahaemolyticus.

Vibrio parahaemolyticus has dual flagellar systems adapted for locomotion under different circumstances. A single, sheathed polar flagellum propels the swimmer cell in liquid environments. Numerous unsheathed lateral flagella move the swarmer cell over surfaces. The polar flagellum is produced continuously, whereas the synthesis of lateral flagella is induced under conditions that impede the function of the polar flagellum, e.g., in viscous environments or on surfaces. Thus, the organism possesses two large gene networks that orchestrate polar and lateral flagellar gene expression and assembly. In addition, the polar flagellum functions as a mechanosensor controlling lateral gene expression. In order to gain insight into the genetic circuitry controlling motility and surface sensing, we have sought to define the polar flagellar gene system. The hierarchy of regulation appears to be different from the polar system of Caulobacter crescentus or the peritrichous system of enteric bacteria but is pertinent to many Vibrio and Pseudomonas species. The gene identity and organization of 60 potential flagellar and chemotaxis genes are described. Conserved sequences are defined for two classes of polar flagellar promoters. Phenotypic and genotypic analysis of mutant strains with defects in swimming motility coupled with primer extension analysis of flagellar and chemotaxis transcription provides insight into the polar flagellar organelle, its assembly, and regulation of gene expression.

Base Sequence↗

PubMed2000

Two novel genes induced by hard-surface contact of Colletotrichum gloeosporioides conidia.

Germinating conidia of many phytopathogenic fungi must differentiate into an infection structure called the appressorium in order to penetrate into their hosts. This differentiation is known to require contact with a hard surface. However, the molecular basis for this requirement is not known. Induction of this differentiation in the avocado pathogen, Colletotrichum gloeosporioides, by chemical signals such as the host's surface wax or the fruit-ripening hormone, ethylene, requires contact of the conidia with a hard surface for about 2 h. To study molecular events triggered by hard-surface contact, we isolated several genes expressed during the early stage of hard-surface treatment by a differential-display method. The genes that encode Colletotrichum hard-surface induced proteins are designated chip genes. In this study, we report the characterization of CHIP2 and CHIP3 genes that would encode proteins with molecular masses of 65 and 64 kDa, respectively, that have no homology to any known proteins. The CHIP2 product would contain a putative nuclear localization signal, a leucine zipper motif, and a heptad repeat region which might dimerize into coiled-coil structure. The CHIP3 product would be a nine-transmembrane-domain-containing protein. RNA blots showed that CHIP2 and CHIP3 are induced by a 2-h hard-surface contact. However, disruption of these genes did not affect the appressorium-forming ability and did not cause a significant decrease in virulence on avocado or tomato fruits suggesting that C. gloeosporioides might have genes functionally redundant to CHIP2 and CHIP3 or that these genes induced by hard-surface contact control processes not directly involved in pathogenesis.

Amino Acid Sequence↗

PubMed2000

Protection against hydrogen peroxide induced injury in renal proximal tubule cell lines by inhibition of poly(ADP-ribose) synthase.

Radicals including superoxide anions, hydrogen peroxide or hydroxyl radicals and NO or peroxynitrite cause the breakage of DNA strands and activation of poly-(ADP-ribose) synthase (PARS). Recent studies showed that inhibition of PARS activity reduces the tissue injury after exposure to oxidative stress. However, the role of PARS in renal injury by oxidants has not been examined. In this study effect of a PARS inhibitor, 3-aminobenamide (3-AB), on injury of opossum kidney or LLC-PK(1) cells by hydrogen peroxide or tert-butyl hydroperoxide (t-BHP) was examined. The exposure of opossum kidney cells to hydrogen peroxide activated PARS and decreased cellular adenosine triphosphate levels in a concentration-dependent manner. Inhibition of PARS with 3-AB prevented the cell death induced by hydrogen peroxide and also prevented adenosine triphosphate depletion. 3-AB did not have hydroxyl radical scavenging effect. In contrast, t-BHP did not affect the PARS activity. The decrease in cellular adenosine triphosphate levels by t-BHP was less than that by hydrogen peroxide. 3-AB failed to prevent the cell death induced by t-BHP. PARS activation after exposure of hydrogen peroxide was inhibited by addition of t-BHP. However, t-BHP showed an additive effect on cell death with hydrogen peroxide. These results indicate that activation of PARS plays an important role in hydrogen peroxide induced injury in opossum kidney cells and that hydrogen peroxide and t-BHP induce cell injury by different mechanisms.

Adenosine Triphosphate↗

PubMed2000

Dexamethasone suppresses tumor necrosis factor-alpha-induced apoptosis in osteoblasts: possible role for ceramide.

Ceramide has been proposed as a second messenger molecule implicated in a variety of biological processes, including apoptosis. Recently, it has been reported that tumor necrosis factor-alpha (TNF-alpha) activates the release of ceramide and that ceramide acts as a mediator for the TNF-alpha-induced stimulation of the binding affinity of nuclear factor-KB (NF-KB), a ubiquitous transcription factor of particular importance in immune and inflammatory responses. In this study we demonstrate that dexamethasone, which reduces the production of ceramide, significantly inhibits TNF-alpha-induced activation of NF-KB, c-Jun N-terminal kinase, also known as stress-activating protein kinase, caspase-3-like cysteine protease, redistribution of cytochrome c, and apoptosis in MC3T3E1 osteoblasts. Compared with TNF-alpha-induced JNK activation, ceramide elicits a more rapid activation of JNK within 30 min. C2-ceramide activates NF-KB and caspase-3 like protease to the same degree and with kinetics similar to those of TNF-alpha. This study provides evidence that the release of ceramide may be required as a second messenger in TNF-alpha-induced apoptosis. These results also suggest a regulatory role for dexamethasone in TNF-alpha-induced apoptosis via inhibition of ceramide release. Therefore, our in vitro results suggest that therapies targeted at the inhibition of ceramide release may abrogate inflammatory processes in TNF-alpha-related diseases, including rheumatoid arthritis and periodontitis.

Animals↗

PubMed2000

Thyrotropin induces SOCS-1 (suppressor of cytokine signaling-1) and SOCS-3 in FRTL-5 thyroid cells.

TSH has multiple physiological roles: it is required for growth, differentiation, and function of the thyroid gland, and it regulates transcription of interferon-gamma (IFN-gamma)-responsive genes in thyrocytes, including genes for the major histocompatibility complex and intercellular adhesion molecule-1. This report demonstrates that TSH induces the expression of suppressor of cytokine signaling (SOCS)-1 and -3 proteins and alters the phosphorylation state of signal transducer and activator of transcription (STAT) proteins STAT1 and STAT3. The expression of SOCS-1 and SOCS-3 and the phosphorylation state of STAT1 and STAT3 were examined after treatment with TSH or IFN-gamma in either TSH-sensitive FRTL-5 thyroid cells or TSH-insensitive FRT and buffalo rat liver (BRL) cells, which lack functional TSH receptors. SOCS-1 and SOCS-3 are constitutively expressed in FRTL-5 cells, but not in FRT and BRL cells. IFN-gamma up-regulated SOCS-1 and SOCS-3 RNA and protein in FRTL-5 cells, as reported previously for nonthyroid cells. Interestingly, TSH also significantly induced SOCS-1 and SOCS-3 in FRTL-5 cells, but not in FRT and BRL cells. When SOCS-1 or SOCS-3 was overexpressed in FRTL-5 cells, STAT1 phosphorylation at Y701 and STAT1/DNA complex formation in response to IFN-gamma were reduced. Furthermore, overexpression of either SOCS-1 or SOCS-3 significantly inhibited the IFN-gamma-mediated transactivation of the rat ICAM-1 (intercellular adhesion molecule-1) promoter. TSH and IFN-gamma had different effects on STAT1 and STAT3 phosphorylation. The phosphorylation of Y701 in STAT1, which is responsible for homodimer formation, nuclear translocation, and DNA binding, was specifically stimulated by IFN-gamma, but not by TSH or forskolin. However, the phosphorylation of S727 in STAT1 was induced by IFN-gamma, TSH, and forskolin. TSH induced phosphorylation of both Y705 and S727 in STAT3, while IFN-gamma phosphorylated only the Y705. In addition, we found that SOCS-3 was associated with JAK1 and JAK2 and that these associations were stimulated by TSH. These findings demonstrate that TSH induces SOCS in thyroid cells and provides the evidence of signal cross-talk between TSH and cytokines in thyroid cells.

Animals↗

PubMed2000

Involvement of JAK/STAT (Janus kinase/signal transducer and activator of transcription) in the thyrotropin signaling pathway.

TSH is an important physiological regulator of growth and function in thyroid gland. The mechanism of action of TSH depends on interaction with its receptor coupled to heterotrimeric G proteins. We show here that TSH induces the phosphorylation of tyrosine in the intracellular kinases Janus kinase 1 (JAK1) and -2 (JAK2) in rat thyroid cells and in Chinese hamster ovary (CHO) cells transfected with human TSH receptor (TSHR). The JAK family substrates STAT3 (signal transducers and activators of transcription) are rapidly tyrosine phosphorylated in response to TSH. We also find that JAK1, JAK2, and STAT3 coprecipitate with the TSHR, indicating that the TSHR may be able to signal through the intracellular phosphorylation pathway used by the JAK-STAT cascade. TSH increases STAT3-mediated promoter activity and also induces endogenous SOCS-1 (suppressor of cytokine signaling-1) gene expression, a known target gene of STAT3. The expression of a dominant negative form of STAT3 completely inhibited TSH-mediated SOCS-1 expression. These findings suggest that the TSHR is able to signal through JAK/STAT3 pathways.

Animals↗