T Jippo

Publications (28)172.66 Total impact

• Article: Effect of MITF on transcription of transmembrane tryptase gene in cultured mast cells of mice.

  E Morii, H Ogihara, K Oboki, T R Kataoka, T Jippo, Y Kitamura
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  ABSTRACT: Mouse mast cell protease (mMCP)-6, mMCP-7 and transmembrane tryptase (TMT) are all tryptases. The normal mi transcription factor (+-MITF) transactivated mMCP-6 gene by binding three consensus motifs in the promoter region, but no MITF-binding motifs were found in the mMCP-7 promoter. Instead, c-Jun transactivated mMCP-7 gene, and +-MITF cooperated with it. The mi-MITF encoded by mutant mi allele inhibited the transactivation by c-Jun and reduced the mMCP-7 promoter activity. Here, the effect of MITF on the TMT gene expression was examined. The +-MITF enhanced the TMT promoter activity by binding two consensus motifs. The mi-MITF showed the inhibitory effect on TMT gene expression. The effect of +-MITF on TMT gene was similar to the effect on mMCP-6 gene, and that of mi-MITF was similar to the effect on mMCP-7 gene. The effects of MITF on TMT gene appeared distinct from its effects on either mMCP-6 or mMCP-7 gene.
  Biochemical and Biophysical Research Communications 01/2002; 289(5):1243-6. · 2.48 Impact Factor
• Article: Tissue-dependent alteration of protease expression phenotype in murine peritoneal mast cells that were genetically labeled with green fluorescent protein.

  T Jippo, Y M Lee, Y Ge, D K Kim, M Okabe, Y Kitamura
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  ABSTRACT: The changing process of protease expression phenotype was studied after transplantation of peritoneal mast cells (PMCs). To pursue the fate of the transplanted PMCs, we obtained PMCs from WBB6F(1)-c-kit(+)/c-kit(+) mice with a transgene encoding green fluorescent protein (GFP). A large (n = 10(4)) or small (n = 500) number of PMCs was injected into the stomach wall of genetically mast cell-deficient WBB6F(1)-c-kit(W)/c-kit(Wv) mice without the GFP transgene. The original PMCs expressed messenger (m) RNAs of both mast cell carboxypeptidase A (MC-CPA) and mouse mast cell protease (mMCP)-2. The MC-CPA(+)/mMCP-2(+) phenotype did not change in both the muscularis propria and mucosa when 10(4) PMCs were injected. In contrast, when 500 PMCs were injected, the mast cells that developed in the muscularis propria showed MC-CPA(+)/mMCP-2(-) phenotype and those that appeared in the mucosa showed MC-CPA(-)/mMCP-2(+) phenotype. On day 1 after the injection of 500 PMCs, only approximately 20 GFP(+) cells were detected in the muscularis propria and no GFP(+) cells in the mucosa. The proportion of Alcian blue(+) cells decreased until day 7 and increased thereafter. The GFP(+) but Alcian blue(-) cells were considered as degranulated PMCS: The remarkable decrease or degranulation seemed to be necessary for the alteration of protease expression phenotype.
  American Journal Of Pathology 06/2001; 158(5):1695-701. · 4.89 Impact Factor
• Article: Importance of leucine zipper domain of mi transcription factor (MITF) for differentiation of mast cells demonstrated using mi(ce)/mi(ce) mutant mice of which MITF lacks the zipper domain.

  E Morii, H Ogihara, D K Kim, A Ito, K Oboki, Y M Lee, T Jippo, S Nomura, K Maeyama, M L Lamoreux, Y Kitamura
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  ABSTRACT: The mi transcription factor (MITF) is a basic helix-loop-helix leucine zipper (bHLH-Zip) transcription factor that is important for the development of mast cells. Mast cells of mi/mi genotype express normal amount of abnormal MITF (mi-MITF), whereas mast cells of tg/tg genotype do not express any MITFs. Mast cells of mi/mi mice show more severe abnormalities than those of tg/tg mice, indicating that the mi-MITF possesses the inhibitory function. The MITF encoded by the mi(ce) mutant allele (ce-MITF) lacks the Zip domain. We examined the importance of the Zip domain using mi(ce)/mi(ce) mice. The amounts of c-kit, granzyme B (Gr B), and tryptophan hydroxylase (TPH) messenger RNAs decreased in mast cells of mi(ce)/mi(ce) mice to levels comparable to those of tg/tg mice, and the amounts were intermediate between those of +/+ mice and those of mi/mi mice. Gr B mediates the cytotoxic activity of mast cells, and TPH is a rate-limiting enzyme for the synthesis of serotonin. The cytotoxic activity and serotonin content of mi(ce)/mi(ce) mast cells were comparable to those of tg/tg mast cells and were significantly higher than those of mi/mi mast cells. The phenotype of mi(ce)/mi(ce) mast cells was similar to that of tg/tg mast cells rather than to that of mi/mi mast cells, suggesting that the ce-MITF had no functions. The Zip domain of MITF appeared to be important for the development of mast cells. (Blood. 2001;97:2038-2044)
  Blood 05/2001; 97(7):2038-44. · 9.90 Impact Factor
• Article: Independent influence of strain difference and mi transcription factor on the expression of mouse mast cell chymases.

  Y Ge, T Jippo, Y M Lee, S Adachi, Y Kitamura
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  ABSTRACT: Expression of mouse mast cell protease (mMCP) genes was examined with particular attention to the transactivation effect of mi transcription factor (MITF) and the expression differences between C57BL/6 (B6) and WB strains. We had reported the enhancing effect of MITF on the expression of mMCP-4, -5, and -6 genes in cultured mast cells (CMCs) of B6 strain, and in the present study we demonstrated the enhancing effect on the expression of mMCP-2 and -9 genes as well. The enhancing effect of MITF on the expression of mMCP-2, -4, -5, -6, and -9 genes was also detected in CMCs of the WB strain. The regulation of mMCP-2, -4, and -9 genes was localized to a specific promoter element (CANNTG) which was recognized and bound by MITF and which was conserved between the B6 and WB strains. On the other hand, the expression of mMCP-2, -4, and -9 genes was smaller in CMCs of the B6 strain when compared to their expression in CMCs of the WB strain. Although mMCP-5 is a chymase as mMCP-2, -4, and -9, and genes encoding all of the chymases are located on chromosome 14, the mMCP-5 gene was regulated in a manner distinct from mMCP-2, -4, and -9 genes.
  American Journal Of Pathology 02/2001; 158(1):281-92. · 4.89 Impact Factor
• Article: mi-transcription factor as a regulator of mast cell differentiation.

  Y Kitamura, E Morii, T Jippo, A Ito
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  ABSTRACT: Masts cells are progeny of the hematopoietic stem cell. For the differentiation of mast cells, a transcription factor encoded by the mouse mi locus (MITF) plays an important role. The expression of many genes encoding proteins that are essential for the function of mast cells is regulated by MITF. Because various mutant mice are available at the mi locus and because cultured mast cells are easily obtained from the spleen of these mutant mice, this system may be a good model for studying the regulation of hematopoietic cell differentiation by a transcription factor.
  International Journal of Hematology 05/2000; 71(3):197-202. · 1.27 Impact Factor
• Article: Involvement of mi-transcription factor in expression of alpha-melanocyte-stimulating hormone receptor in cultured mast cells of mice.

  S Adachi, E Morii, D k Kim, H Ogihara, T Jippo, A Ito, Y M Lee, Y Kitamura
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  ABSTRACT: The microphthalmia (mi) locus encodes a member of the basic-helix-loop-helix-leucine zipper (bHLH-Zip) protein family of transcription factors (MITF). We have reported that expression of several genes was impaired in cultured mast cells (CMCs) of mi/mi mice due to a defective transactivation ability of mutant MITF (mi-MITF). We also found that mi/mi CMCs did not express a receptor (MC1R) for alpha-melanocyte-stimulating hormone. The overexpression of the wild-type (+/+) MITF but not mi-MITF normalized the expression of the MC1R in mi/mi CMCs, indicating the involvement of +-MITF in the MC1R gene expression. Next, we analyzed the promoter region of the MC1R gene by the transient cotransfection assay. The luciferase construct under the control of the MC1R promoter and the cDNA-encoding +-MITF or mi-MITF were cotransfected into NIH/3T3 fibroblasts. The cotransfection of +-MITF but not mi-MITF increased the luciferase activity. There were five CANNTG motifs recognized by bHLH-Zip-type transcription factors in the cloned promoter region. We found +-MITF bound two of five CANNTG motifs, and both motifs were essential for the transactivation of the MC1R gene by +-MITF. These results indicated that +-MITF directly transactivated the MC1R gene through these two motifs.
  The Journal of Immunology 02/2000; 164(2):855-60. · 5.79 Impact Factor
• Article: Inhibitory effect of mast cell-mediated immediate-type allergic reactions by Cichorium intybus.

  H M Kim, H W Kim, Y S Lyu, J H Won, D K Kim, Y M Lee, E Morii, T Jippo, Y Kitamura, N H An
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  ABSTRACT: We investigated the effect of an aqueous extract of Cichorium intybus (CIAE) on mast cell-mediated immediate type allergic reactions. CIAE (0.1-1000 mg kg-1) dose-dependently inhibited systemic anaphylactic reaction induced by compound 48/80 in mice. Especially, CIAE inhibited compound 48/80-induced anaphylactic reaction 100% with the dose of 1000 mg kg-1. CIAE 1000 mg kg-1also significantly inhibited local anaphylactic reaction activated by anti-dinitrophenyl (DNP) IgE. When mice were pretreated with CIAE at a concentration ranging from 0.1 to 1000 mg kg-1, the plasma histamine levels were reduced in a dose-dependent manner. CIAE (1-1000 microg ml-1) dose-dependently inhibited histamine release from the rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. The level of cAMP in RPMC, when CIAE (1000 microg ml-1) was added, increased significantly compared with that of control cells. These results indicate that CIAE inhibits mast cell-mediated immediate-type allergic reactions in vivo and in vitro.
  Pharmacological Research 08/1999; 40(1):61-5. · 4.44 Impact Factor
• Article: Different effect of various mutant MITF encoded by mi, Mior, or Miwh allele on phenotype of murine mast cells.

  D K Kim, E Morii, H Ogihara, Y M Lee, T Jippo, S Adachi, K Maeyama, H M Kim, Y Kitamura
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  ABSTRACT: The mi locus encodes a member of the basic-helix-loop-helix-leucine zipper protein family of transcription factors (hereafter called MITF). Mutant alleles of mi, Mior, and Miwh are deletion or point mutation of the basic domain by which MITF binds DNA. The basic domain also has nuclear localization potential. In the present study, we compared the mast cell abnormalities of Mior/Mior and Miwh/Miwh mice with those of mi/mi mice, of which many have been described by us. The number of mast cells in the skin of Mior/Mior suckling mice was remarkably decreased from that observed in mi/mi suckling mice, but the number was normal in the skin of Miwh/Miwh suckling mice. The decrease in skin mast cells was more severe in the mi/mi embryos than in mi/mi suckling mice, but the magnitude of the decrease was comparable between Mior/Mior embryos and Mior/Mior suckling mice. The poor mRNA expression of granzyme B and tryptophan hydroxylase genes was observed in all cultured mast cells (CMCs) derived from the spleens of Miwh/Miwh, Mior/Mior, and mi/mi mice. However, the poor expression of mouse mast cell protease-4 (MMCP-4), MMCP-5, and MMCP-6 was observed only in Mior/Mior and mi/mi CMCs. MITF encoded by Miwh mutant allele (Miwh-MITF) showed deficient but demonstratable DNA binding, but mi-MITF and Mior-MITF did not show any DNA binding ability. Although Miwh-MITF and Mior-MITF showed normal nuclear localization potential, the potential was significantly impaired in mi-MITF. The rank order of mast cell abnormality (mi/mi > Mior/Mior > Miwh/Miwh) appears to be related to the functional abnormality of MITF encoded by each mutant gene.
  Blood 06/1999; 93(12):4179-86. · 9.90 Impact Factor
• Article: Deficient transcription of mouse mast cell protease 4 gene in mutant mice of mi/mi genotype.

  T Jippo, Y M Lee, Y Katsu, K Tsujino, E Morii, D K Kim, H M Kim, Y Kitamura
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  ABSTRACT: The mi locus encodes a member of the basic-helix-loop-helix-leucine zipper (bHLH-Zip) protein family of transcription factors (hereafter called MITF). We reported that expression of the mouse mast cell protease 5 (MMCP-5) and MMCP-6 genes were deficient in cultured mast cells (CMC) derived from mutant mice of mi/mi genotype. Despite the reduced expression of both MMCP-5 and MMCP-6, their regulation mechanisms were different. Because MMCP-5 is a chymase and MMCP-6 a tryptase, there was a possibility that the difference in regulation mechanisms was associated with their different characteristics as proteases. We compared the regulation mechanisms of another chymase, MMCP-4, with those of MMCP-5 and MMCP-6. The expression of the MMCP-4 gene was also deficient in mi/mi CMC. The overexpression of the normal (+) MITF but not of mi-MITF normalized the poor expression of the MMCP-4 gene in mi/mi CMC, indicating the involvement of +-MITF in transactivation of the MMCP-4 gene. Although MMCP-4 is chymase as MMCP-5, the regulation of MMCP-4 expression was more similar to MMCP-6 than to MMCP-5. We also showed the deficient expression of granzyme B and cathepsin G genes in mi/mi CMC. Genes encoding granzyme B, cathepsin G, MMCP-4, and MMCP-5 are located on chromosome 14. Because all these genes showed deficient expression in mi/mi CMC, there is a possibility that MITF might regulate the expression of these genes through a locus control region.
  Blood 04/1999; 93(6):1942-50. · 9.90 Impact Factor
• Article: Inhibitory effect of the transcription factor encoded by the mi mutant allele in cultured mast cells of mice.

  A Ito, E Morii, D K Kim, T R Kataoka, T Jippo, K Maeyama, H Nojima, Y Kitamura
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  ABSTRACT: The mi locus of mice encodes a transcription factor of the basic-helix-loop-helix-leucine zipper protein family (MITF). The MITF encoded by the mutant mi allele (mi-MITF) deletes 1 of 4 consecutive arginines in the basic domain. The mice of mi/mi genotype express mi-MITF, whereas the mice of tg/tg genotype have a transgene at the 5' flanking region of the mi gene and do not express any MITF. To investigate the function of mi-MITF in cultured mast cells (CMCs), we took two approaches. First, mRNA obtained from mi/mi CMCs or tg/tg CMCs was subtracted from complementary (c) DNA library of normal (+/+) CMCs, and the (+/+-mi/mi) and (+/+-tg/tg) subtraction libraries were obtained. When the number of clones that hybridized more efficiently with +/+ CMC cDNA probe than with mi/mi or tg/tg CMC cDNA probe was compared using Southern analysis, the number was larger in the (+/+-mi/mi) library than in the (+/+-tg/tg) library. Second, we compared mRNA expression of six genes between mi/mi and tg/tg CMCs by Northern analysis. The transcription of three genes encoding mouse mast cell proteases was impaired in both mi/mi and tg/tg CMCs. On the other hand, the transcription of three genes encoding c-kit receptor, tryptophan hydroxylase, and granzyme B was markedly reduced in mi/mi CMCs, but the reduction was significantly smaller in tg/tg CMCs. These results indicated the inhibitory effect of mi-MITF on the transactivation of particular genes in CMCs.
  Blood 03/1999; 93(4):1189-96. · 9.90 Impact Factor
• Article: Impaired expression of integrin alpha-4 subunit in cultured mast cells derived from mutant mice of mi/mi genotype.

  D K Kim, E Morii, H Ogihara, K Hashimoto, K Oritani, Y M Lee, T Jippo, S Adachi, Y Kanakura, Y Kitamura
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  ABSTRACT: The mi locus encodes a member of the basic-helix-loop-helix-leucine zipper protein family of transcription factors (hereafter called MITF). We have reported that expression of several genes was impaired in cultured mast cells (CMCs) of mi/mi mice due to a defective transactivation ability of mutant MITF (mi-MITF). Because attachment of mi/mi CMCs to fibroblasts is impaired, we examined the expression of integrin genes in mi/mi CMCs in the present study. Among the integrin genes examined, the expression of integrin alpha4 subunit was barely detectable in mi/mi CMCs, and the alpha4 protein was not detected by flow cytometry either. The specific adhesion to vascular cell adhesion molecule-1 (VCAM-1), the ligand for alpha4 subunit, was observed in +/+ CMCs but not in mi/mi CMCs, indicating that the expression of integrin alpha4 subunit at a functional level did not occur in mi/mi CMCs. In the promoter region of the alpha4 subunit gene, there was a CACTTG motif to which normal MITF (+- MITF) bound. The coexpression of +-MITF but not of mi-MITF transactivated the promoter of the alpha4 subunit gene. The deletion or mutation of the CACTTG motif abolished the transactivation by +-MITF, suggesting that +-MITF directly transactivated the gene encoding alpha4 subunit of integrin.
  Blood 10/1998; 92(6):1973-80. · 9.90 Impact Factor
• Article: Alteration of protease expression phenotype of mouse peritoneal mast cells by changing the microenvironment as demonstrated by in situ hybridization histochemistry.

  Y M Lee, T Jippo, D K Kim, Y Katsu, K Tsujino, E Morii, H M Kim, S Adachi, Y Nawa, Y Kitamura
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  ABSTRACT: Mouse mast cell protease (MMCP) mRNA expression was examined by in situ hybridization histochemistry. Peritoneal mast cells (PMCs) of WBB6F1-(+/+) mice expressed MMCP-2, MMCP-4, MMCP-5, and MMCP-6 mRNAs, but did not express MMCP-1 mRNA. When proliferation of PMCs was induced by culturing them in methylcellulose with T cell-derived cytokines, cells in mast cell colonies expressed MMCP-1 mRNA. These mast cells were transferred to a suspension culture to induce further proliferation. The phenotype of the resulting PMC-derived cultured mast cells was similar to that of bone marrow-derived cultured mast cells. When 10(5) PMC-derived cultured mast cells or 10(5) bone marrow-derived cultured mast cells were injected into the stomach wall of mast cell-deficient WBB6F1-W/Wv mice, mast cells that appeared in the mucosa and muscularis propria were similar to mast cells in the stomach of intact WBB6F1-(+/+) mice, indicating the injected cells adapted to a new tissue environment. In contrast, when 10(5) PMCs were injected into the stomach wall of WBB6F1-W/Wv mice, the injected PMCs did not adapt to the mucosa. When 20 PMCs were injected, they proliferated and adapted to the mucosal environment. The present results suggest that PMCs adapt to new environments when proliferation occurs before redifferentiation.
  American Journal Of Pathology 10/1998; 153(3):931-6. · 4.89 Impact Factor
• Article: Inhibition of immediate type allergic reactions by the aqueous extract of Kum-Hwang-San.

  H Kim, H Shin, E Lee, J Lee, J Jung, N An, Y Lee, D Kim, T Jippo, Y Kitamura
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  ABSTRACT: We studied the effect of aqueous extract of Kum-Hwang-San (KHS) on mast cell-mediated immediate type allergic reactions. KHS (1-100 microg/site) inhibited concentration-dependently mast cell-dependent ear swelling response induced by compound 48/80 (200 microg/site) in mice by both topical and intradermal application. KHS (0.1-100 microg/site) inhibited concentration-dependently passive cutaneous anaphylaxis induced by anti-dinitrophenyl (DNP) IgE in rats by both topical and intradermal application. KHS also inhibited concentration-dependently the histamine release from the rat peritoneal mast cells (RPMC) by compound 48/80 and anti-DNP IgE. Moreover, KHS had a significant inhibitory effect on anti-DNP IgE-induced tumor necrosis factor-alpha (TNF-alpha) secretion from RPMC. These results indicate that KHS inhibits immediate type allergic reactions by inhibition of histamine release and TNF-alpha secretion from mast cells in vivo and in vitro.
  International Journal of Immunopharmacology 07/1998; 20(6):285-94.
• Article: Systematic method to obtain novel genes that are regulated by mi transcription factor: impaired expression of granzyme B and tryptophan hydroxylase in mi/mi cultured mast cells.

  A Ito, E Morii, K Maeyama, T Jippo, D K Kim, Y M Lee, H Ogihara, K Hashimoto, Y Kitamura, H Nojima
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  ABSTRACT: The mi locus encodes a member of the basic-helix-loop-helix-leucine zipper protein family of transcription factors (hereafter called MITF). We have reported that the expression of several genes was impaired in cultured mast cells (CMCs) of mi/mi genotype, and demonstrated the involvement of MITF in the transcription of these genes. To obtain new genes whose transcription may be regulated by MITF, we prepared a subtracted cDNA library using +/+ and mi/mi CMCs. We found two clones carrying the granzyme (Gr) B and tryptophan hydroxylase (TPH) cDNAs in the subtracted library. The expression of the Gr B and TPH genes decreased in mi/mi CMCs, and recovered to nearly normal level by the overexpression of normal (+) MITF but not of mutant (mi) MITF. The +-MITF bound three and one CANNTG motifs in the Gr B and TPH promoters, respectively, and transactivated these two genes, indicating the involvement of +-MITF in their expression. Because TPH is the rate-limiting enzyme for serotonin synthesis, we examined the serotonin content of +/+ and mi/mi CMCs. The serotonin content was significantly smaller in mi/mi CMCs than in +/+ CMCs. The introduction of +-MITF but not of mi-MITF normalized the serotonin content in mi/mi CMCs.
  Blood 06/1998; 91(9):3210-21. · 9.90 Impact Factor
• Article: Delayed onset of hemolytic anemia in CBA-Pk-1slc/Pk-1slc mice with a point mutation of the gene encoding red blood cell type pyruvate kinase.

  K Tsujino, H Kanno, K Hashimoto, H Fujii, T Jippo, E Morii, Y M Lee, H Asai, S Miwa, Y Kitamura
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  ABSTRACT: The Pk-1slc gene encodes a mutant red blood cell (RBC) type pyruvate kinase (PK), and adult CBA-Pk-1slc/Pk-1slc mice show a severe nonspherocytic hemolytic anemia. However, the number of RBCs and the proportion of reticulocytes were comparable between neonatal CBA-Pk-1slc/Pk-1slc mice and control -+/+ mice. Since the age-dependent increase of RBCs was much greater in CBA-+/+ mice than in CBA-Pk-1slc/Pk-1slc mice, significant anemia was observed in the latter mice on day 14 after birth. The increase of RBCs in CBA-+/+ mice was due to the prolongation of their survival time. The half life of RBCs increased in CBA-+/+ mice with ages, but it decreased in CBA-Pk-1slc/Pk-1slc mice. The relatively longer half life of RBCs in neonatal CBA-Pk-1slc/Pk-1slc mice appeared to be due to the delayed switching from M2-type PK that are expressed by undifferentiated erythroid precursor cells to RBC-type PK that are expressed by mature RBCs.
  Blood 04/1998; 91(6):2169-74. · 9.90 Impact Factor
• Article: Abnormal expression of mouse mast cell protease 5 gene in cultured mast cells derived from mutant mi/mi mice.

  E Morii, T Jippo, T Tsujimura, K Hashimoto, D K Kim, Y M Lee, H Ogihara, K Tsujino, H M Kim, Y Kitamura
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  ABSTRACT: Mast cells contain a lot of mast cell-specific proteases. We have reported that the expression of mouse mast cell protease 6 (MMCP-6) is remarkably reduced in both cultured mast cells (CMCs) and skin mast cells of mi/mi mutant mice. In the present study, we found that the expression of MMCP-5 was reduced in CMCs but not in skin mast cells of mi/mi mice, and we compared the regulation mechanisms of MMCP-5 with those of MMCP-6. The mi locus encodes a member of the basic-helix-loop-helix-leucine zipper (bHLH-Zip) protein family of transcription factors (hereafter called MITF). The consensus sequence recognized and bound by bHLH-Zip transcription factors is CANNTG. The overexpression of the normal (+) MITF but not of mi-MITF normalized the poor expression of the MMCP-5 gene in mi/mi CMCs, indicating the involvement of +-MITF in transactivation of the MMCP-5 gene. Although +-MITF directly bound CANNTG motifs in the promoter region of the MMCP-6 gene and transactivated it, the binding of +-MITF to the CAGTTG motif in the promoter region of the MMCP-5 gene was not detectable. The +-MITF appeared to regulate the transactivation of the MMCP-5 gene indirectly. Moreover, addition of stem cell factor to the medium normalized the expression of the MMCP-5 but not of the MMCP-6 gene in mi/mi CMCs. Despite the significant reduction of both MMCP-5 and MMCP-6 expressions in mi/mi CMCs, their regulation mechanisms appeared to be different.
  Blood 11/1997; 90(8):3057-66. · 9.90 Impact Factor
• Article: Involvement of transcription factor encoded by the mouse mi locus (MITF) in expression of p75 receptor of nerve growth factor in cultured mast cells of mice.

  T Jippo, E Morii, K Tsujino, T Tsujimura, Y M Lee, D K Kim, H Matsuda, H M Kim, Y Kitamura
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  ABSTRACT: The mi locus of mice encodes a member of the basic-helix-loop-helix-leucine zipper (bHLH-Zip) protein family of transcription factors (hereafter called MITF). Cultured mast cells (CMCs) of mi/mi genotype showed a poor response to nerve growth factor (NGF). Addition of NGF to the suboptimal dose of interleukin-3 (IL-3) increased the plating efficiency of normal (+/+) CMCs but not mi/mi CMCs. Although +/+ CMCs were berberine sulfate-negative when cultured with IL-3, +/+ CMCs became berberine sulfate-positive when cultured in the presence of both IL-3 and NGF, which suggested increased heparin content. In contrast, NGF did not influence the phenotype of mi/mi CMCs. The poor response of mi/mi CMCs to NGF was attributed to the deficient expression of p75 NGF receptor. The purpose of the present study is to examine the effect of MITF on p75 gene transcription. Overexpression of +-MITF or mi-MITF was observed in mi/mi CMCs to which cDNA encoding each type of MITF had been introduced using the retroviral vector. Overexpression of +-MITF but not of mi-MITF normalized the expression of p75 and the above-mentioned poor responses of mi/mi CMCs to NGF, indicating the involvement of +-MITF in p75 gene transactivation. Then, we analyzed the promoter of the p75 gene. Two CANNTG motifs recognized by bHLH-Zip-type transcription factors were conserved between the mouse and rat p75 promoters. One of these two CANNTG motifs was specifically bound by +-MITF. When the luciferase gene under the control of the p75 promoter was cotransfected into NIH/3T3 fibroblasts with cDNA encoding +-MITF or mi-MITF, luciferase activity increased significantly only when +-MITF cDNA was cotransfected. The mutation of this CANNTG motif abolished the transactivation effect of +-MITF, indicating that +-MITF transactivated the p75 gene, at least in part, through direct binding.
  Blood 11/1997; 90(7):2601-8. · 9.90 Impact Factor
• Article: [Biology of mast cells ad basophils].

  Y Kitamura, T Jippo
  Arerugī = [Allergy] 11/1997; 46(10):1003-6.
• Article: Establishment and characterization of cell lines derived from a transplantable rat malignant meningioma: morphological heterogeneity and production of nerve growth factor.

  K Tsujino, J Yamate, Y Tsukamoto, D Kumagai, Y Kannan, T Jippo, M Kuwamura, T Kotani, M Takeya, S Sakuma
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  ABSTRACT: A cell line (KMY-J) was established from a transplantable tumor (MM-KMY) derived from a spontaneous malignant meningioma arising in an aged F344 rat, and three cloned cell lines (KMY-1, KMY-2 and KMY-3) were induced from the parent KMY-J. Morphologically, KMY-J and tumors induced in syngeneic rats by KMY-J showed cell pleomorphism. All neoplastic cells in KMY-J and its tumors were immunoreactive to vimentin; occasional cells reacted to ED1 (rat macrophage/histiocyte-specific antibody) and alpha-smooth muscle actin (alpha-SMA), indicating expression of histiocytic or myofibroblastic immunophenotypes of meningioma cells. In contrast, KMY-1, KMY-2 and KMY-3 consisted of a uniform cell population differing from each other. KMY-1-induced tumors were similar histologically to meningeal fibrosarcomas. Dendritic cells seen in KMY-2 cultures gave an appearance of arachnoid trabecular cells. In KMY-3 and its tumors, large round cells and multinucleated giant cells were predominant. Cells of these cloned cell lines also reacted to vimentin, but were negative for ED1 and alpha-SMA. By the bioassay using PC12 cells and reverse transcription-polymerase chain reaction for nerve growth factor (NGF) mRNA, production of NGF was demonstrated in the parent and cloned cell lines. The present cell lines may prove useful for studying the histological features of meningeal tumors and the bioactive factors produced by meningeal cells.
  Acta Neuropathologica 06/1997; 93(5):461-70. · 9.32 Impact Factor
• Article: Expression of mast-cell-specific proteases in tissues of mice studied by in situ hybridization.

  T Jippo, K Tsujino, H M Kim, D K Kim, Y M Lee, Y Nawa, Y Kitamura
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  ABSTRACT: The protease mRNA expression phenotype of individual mast cells was studied by in situ hybridization. Mouse mast cell protease (MMCP)-2 mRNA was expressed by mast cells located in the mucosa of the stomach of WB(-)+/+ and (WB x C57BL/6)F1(-)+/+ (hereafter WBB6F1(-)+/+) mice but not by mast cells in the same tissue of C57BL/ 6(-)+/+ mice. Even in the stomach of WBB6F1(-)+/+ mice, mast cells located in the muscularis propria did not express MMCP-2 mRNA. The mRNAs of MMCP-4 and mouse mast cell carboxypeptidase A were not expressed by mast cells in the stomach mucosa of untreated WBB6F1(-)+/+ mice but were expressed after the infection of Strongyloides venezuelensis. We examined whether MMCP-2 mRNA expression varied by changing environments of mast cells. Cultured mast cells of WBB6F1(-)+/+ mice that expressed MMCP-2 mRNA were transplanted into the stomach wall of genetically mast-cell-deficient WBB6F1(-)W/Wv mice. Mast cells that appeared in the mucosa expressed the MMCP-2 mRNA, but mast cells that appeared in the muscularis propria did not, indicating the adaptation of cultured mast cells into a new environment. In contrast to cultured mast cells, peritoneal mast cells of WBB6F1(-)+/+ mice that expressed MMCP-2 mRNA as well did not adapt to the muscularis propria of WBB6F(1)-W/Wv mice. The MMCP-2 mRNA remained to be expressed after the settlement in either the mucosa or the muscularis propria. Furthermore, the peritoneal mast cells did not change the MMCP-4 and MMCP-6 mRNA expression phenotype after the settlement in either the mucosa or the muscularis propria of WBB6F(1)-W/Wv mice. The present result indicated that both intracellular factors such as strain specificity and source of mast cells and extracellular factors such as tissue specificity and helminth infection influenced the protease expression phenotypes.
  American Journal Of Pathology 05/1997; 150(4):1373-82. · 4.89 Impact Factor