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Differential Effects of Transforming Growth Factor-β1, a Fibrogenic Factor, on Macrophage-Like Cells (HS-P) and Myofibroblastic Cells (MT-9) In Vitro

Department of Veterinary Pathology, Graduate School of Agriculture and Biological Science, Osaka Prefecture University, Gakuencho 1-1, Sakai, Osaka 599-8531, Japan, yamate{at}vet.osakafu-u.ac.jp

Masaru Maeda

Department of Veterinary Pathology, Graduate School of Agriculture and Biological Science, Osaka Prefecture University, Gakuencho 1-1, Sakai, Osaka 599-8531, Japan

Sally J. Benn

Department of Biomedical Sciences, University of Guelph, Guelph, Ontario, N1G2W1, Canada

James E. Laithwaite

Department of Biomedical Sciences, University of Guelph, Guelph, Ontario, N1G2W1, Canada

Alison Allan

Department of Biomedical Sciences, University of Guelph, Guelph, Ontario, N1G2W1, Canada

Mika Ide

Department of Veterinary Pathology, Graduate School of Agriculture and Biological Science, Osaka Prefecture University, Gakuencho 1-1, Sakai, Osaka 599-8531, Japan

Mitsuru Kuwamura

Department of Veterinary Pathology, Graduate School of Agriculture and Biological Science, Osaka Prefecture University, Gakuencho 1-1, Sakai, Osaka 599-8531, Japan

Takao Kotani

Department of Veterinary Pathology, Graduate School of Agriculture and Biological Science, Osaka Prefecture University, Gakuencho 1-1, Sakai, Osaka 599-8531, Japan

Sadashige Sakuma

Department of Veterinary Pathology, Graduate School of Agriculture and Biological Science, Osaka Prefecture University, Gakuencho 1-1, Sakai, Osaka 599-8531, Japan

Jonathan Lamarre

Department of Biomedical Sciences, University of Guelph, Guelph, Ontario, N1G2W1, Canada

Transforming growth factor- β1 (TGF-β1) produced by infiltrating macrophages plays a role in fibrotic disorders through the induction of myofibroblasts. To explore possible mechanisms by which TGF-β1 may act in this context, we investigated effects of TGF-β1 on macrophage-like (HS-P) and myofibroblastic (MT-9) cells, two novel cell lines developed by us. Immunocytochemicall y, the addition of TGF-β1 (0, 0.1, 0.5, and 1.0 ng/ml) dose-dependently suppressed the expressions of antigens recognized by macrophage/histiocyte-specific antibodies (ED1 and ED2) in HS-P cells, whereas the addition concomitantly increased the number of anti--smooth muscle actin antibody-positive myofibroblastic cells, suggesting a possible phenotypical modulation of macrophages into myofibroblasts in the fibrotic lesions. By contrast, MT-9 cells did not show such immunophenotypica l changes following TGF-β1 addition. DNA synthesis, measured by tritiated thymidine-incorporation , was inhibited in a dose-dependen tmanner in MT-9 cells by TGF-β1 addition (0, 0.1, 0.2, 0.5, 1.0, 5, and 10 ng/ml), but that in HS-P cells was unchanged. Northern blot analysis revealed that expressions of cell cycle-related early genes, c-jun and c-myc, were increased in HS-P cells after TGF- β1 (1 ng/ml) addition, with c-jun showing peak expression prior to c-myc. By contrast, the peak expressions of c-jun and c-myc were delayed in TGF-β1 (1 ng/ml)-added MT-9 cells, and their levels were less in MT-9 cells than in HS-P cells. Furthermore, TGF-β1 (1 and 10 ng/ml) induced DNA laddering in MT-9 cells, but did not in HS-P cells. Based on these findings, it was speculated that TGF- β1 could have induced G1 arrest in cell cycle and apoptosis in MT-9 cells. The present study showed that there were significant differences in the effects of TGF-β1 between macrophage-like HS-P cells and myofibroblastic MT-9 cells, presumably depending on divergent susceptibilities to TGF- β1 between both cell types. Because such cell types are key cells in the fibrogenesis, HS-P and MT-9 might be useful models for investigating the pathogenesis of fibrosis in vitro.

Key Words: Apoptosis • fibrosis • immediate early genes • macrophage-like cells • myofibroblastic cells • TGF-β1.

References

• Arora PD, McCulloch CA (1999). The deletion of transforming growth factor-β-induced myofibroblasts depends on growth conditions and actin organization. Am J Pathol 155: 2087—2099.[Abstract/Free Full Text]
• Balmain A., Krumlauf R., Vass JK, Birnie GD (1982). Cloning and characterisation of the abundant cytoplasmic 7S RNA from mouse cells. Nucleic Acids Res 10: 4259—4277.[Abstract/Free Full Text]
• Banu N., Meyers CM (1999). TGF-β1 down-regulates induced expression of both class II MHC and B7-1 on primary murine renal tubular epithelial cells. Kidney Int 56: 985—994.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Benn SJ, Allan A., Laithwaite JE, Tsukamoto Y., Yamate J., Kirby G., LaMarre, J. (1998). Effect of extracellular matrix on gene expression and mRNA stability in primary rat hepatocytes. J Toxicol Pathol 11: 219—227.[CrossRef]
• Bhawan J., Majno G. (1989). The myofibroblast. Possible derivation from macrophages in xanthogranuloma. Am J Dermatopathol 11: 255—258.[Web of Science][Medline] [Order article via Infotrieve]
• Boukhalfa G., Desmouliere A., Roudeau E., Gabbiani G., Sraer JD (1996). Relationship between alpha-smooth muscle actin expression and fibrotic changes in human kidney. Exp Nephrol 4: 241—247.[Web of Science][Medline] [Order article via Infotrieve]
• Campbell GR, Ryan GB ( 1983). Origin of myofibroblasts in the avascular capsule around free-floating intraperitoneal blood clots. Pathology 15: 253— 264.[Web of Science][Medline] [Order article via Infotrieve]
• Columbano A., Ledda-Columbano GM, Pibiri M., Piga R., Shinozuka H., De Luca V., Cerignoli F., Tripodi M. (1997). Increased expression of c-fos, c-jun and LRF-1 is not required for in vivo priming of hepatocytes by the mitogen TCPOBOP. Oncogene 14: 857—863.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Cressman DE, Greenbaum LE, DeAngelis RA, Ciliberto G., Furth EE, Poli V., Taub R. ( 1996). Liver failure and defective hepatocyte regeneration in interleukin-6-deficient mice. Science 274: 1379—1383.[Abstract/Free Full Text]
• Damoiseaux JG, Döpp EA, Calame W., Chao D., MacPherson GG, Dijkstra CD (1994). Rat macrophage lysosomal membrane antigen recognized by monoclonal antibody ED1. Immunology 83: 140—147.[Web of Science][Medline] [Order article via Infotrieve]
• Desmouliere A., Redard M., Darby I., Gabbiani G. (1995). Apoptosis mediates the decrease in cellularity during the transition between granulation tissue and scar. Am J Pathol 146: 56—66.[Abstract]
• Diamond JR, Van Goor H., Ding G., Engelmyer E. (1995). Myofibroblasts in experimental hydronephrosis. Am J Pathol 146: 121—129.[Abstract]
• Dijkstra CD, Döpp EA, Joling P., Kraal G. (1985). The heterogeneity of mononuclear phagocytes in lymphoid organs: Distinct macrophage subpopulations in the rat recognized by monoclonal antibodies ED1, ED2 and ED3. Immunology 54: 589—599.[Web of Science][Medline] [Order article via Infotrieve]
• Eddy AA (1994). Protein restriction reduces transforming growth factor-β and interstitital fibrosis in nephrotic syndrome. Am J Physiol 266: F884— F893.[Web of Science][Medline] [Order article via Infotrieve]
• Ehrlich HP, Desmouliere A., Diegelmann RF, Cohen IK, Compton CC, Garner WL, Kapanci Y., Gabbiani G. (1994). Morphological and immunochemical differences between keloid and hypertrophic scar. Am J Pathol 145: 105—113.[Abstract]
• Fan JM, Ng YY, Hill PA, Nikolic-Paterson DJ, Mu W., Atkins RC, Lan H. (1999). Transforming growth factor-beta regulates tubular epithelialmyofibroblast transdifferentition in vitro. Kidney Int 56: 1455—1467.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Gown AM (1990). The mysteries of the myofibroblasts (partially) unmasked. Lab Invest 63: 1—3.[Web of Science][Medline] [Order article via Infotrieve]
• Granville DJ, Carthy CM, Hunt DW, McManus BM (1998). Apoptosis: Molecular aspects of cell death and disease. Lab Invest 78: 893—913.[Web of Science][Medline] [Order article via Infotrieve]
• Guilhot S., Miller T., Cornman G., Isom HC ( 1996). Apoptosis induced by tumor necrosis factor- in rat hepatocyte cell lines expressing hepatitis B virus. Am J Pathol 148: 801—814.[Abstract]
• Hines JE, Johnson SJ, Burt AD ( 1993). In vivo responses of macrophages and perisinusoidal cells to cholestatic liver injury. Am J Pathol 142: 511— 518.[Abstract]
• Hsu JC, Bravo R., Taub R. ( 1992). Interactions among LRF-1, JunB, c-Jun and c-Fos define a regulatory program in the G1 phase of liver regeneration. Mol Cell Biol 12: 4654—4665.[Abstract/Free Full Text]
• Johnson SJ, Hines JE, Burt AD ( 1992). Macrophages and perisinusoidal cell kinetics in acute liver injury. J Pathol 166: 351—358.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Kanzaki T., Kitajima S., Suzumori K. (1991). Biological behavior of cloned cells of human malignant fibrous histiocytoma in vivo and in vitro. Cancer Res 51: 2133—2137.[Abstract/Free Full Text]
• Kliem V., Johnson RJ, Alpers CE, Yoshimura A., Couser WG, Koch KM, Floege J. (1996). Mechanisms involved in the pathogenesi s of tubulointerstitial fibrosis in 5/6-nephrectomized rats. Kidney Int 49: 666—678.[Web of Science][Medline] [Order article via Infotrieve]
• Kuncio GS, Neilson EG, Haverty T. (1991). Mechanisms of tubulointerstitial fibrosis. Kidney Int 39: 550—556.[Web of Science][Medline] [Order article via Infotrieve]
• Laithwaite JE, Benn SJ, Yamate J., FitzGerald DJ, LaMarre J. (1999). Enhanced macrophage resistance to Pseudomonas Exotoxin A is correlated with decreased expression of the low-density lipoprotein receptor-related protein. Infect Immun 67: 5827—5833.[Abstract/Free Full Text]
• Lindahl P., Johansson BR, Leveen P., Betsholtz C. (1997). Pericyte loss and microaneurysm formation in PDGF-B-deficient mice. Science 277: 242— 245.[Abstract/Free Full Text]
• Lin JK, Chou CK ( 1992). In vitro apoptosis in the human hepatoma cell line induces by transforming growth factor-β1. Cancer Res 52: 385— 388.[Abstract/Free Full Text]
• Luttenberger T., Schmid-Kotsas A., Menke A., Siech M., Beger H., Adler G., Grunert A., Bachem MG (2000). Platelet-derived growth factors stimulate proliferation and extracellular matrix synthesis of pancreatic stellate cells: Implications in pathogenesi s of pancreati c fibrosis. Lab Invest 80: 47—55.[Web of Science][Medline] [Order article via Infotrieve]
• Michishita M., Hirayoshi K., Tsuru A., Nakamura N., Yoshida Y., Okuma M., Nagata K. (1991). Effects of type-beta 1 transforming growth factor on the proliferation and differentiation of mouse myelomonocytic leukemia cells (M1). Exp Cell Res 196: 107—113.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Nakatsuji S., Yamate J., Kuwamura M., Kotani T., Sakuma S. (1997). In vivo responses of macrophages and myofibroblasts in the healing following isoproterenol-induced myocardial injury in rats. Virchows Arch 430: 63— 69.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Ng YY, Huang TP, Yang WC, Chen ZP, Yang AH, Mu W., Nikolic-Paterson DJ, Atkins RC, Lan HY (1998). Tubular epithelial-myofibroblast transdifferentiation in progressive tubulointerstitial fibrosis in 5/6 nephrectomized rats. Kidney Int 54: 864—876.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Oka H., Jin L., Kulig E., Scheithauer BW, Lloyd RV (1999). Pituitary adenylate cyclase-activating polypeptide inhibits transforming growth factor-β1induced apoptosis in a human pituitary adenoma cell line. Am J Pathol 155: 1893—1900.[Abstract/Free Full Text]
• Pierce GF, Vande Berg J., Rudolph R., Tarpley J., Mustoe TA (1991). Platelet-derived growth factor-BB and transforming growth factor beta 1 selectively modulate glycosaminoglycans, collagens, and myofibroblasts in excisional wounds. Am J Pathol 138: 629—646.[Abstract]
• Sappino AP, Schurch W., Gabbiani G. (1990). Biology of disease. Differentiation repertoire of fibroblastic cells: Expression of cytoskeletal protein as marker of phenotypic modulations. Lab Invest 63: 144—161.[Web of Science][Medline] [Order article via Infotrieve]
• Schmitt-Graff A., Kruger S., Bochard F., Gabbiani G., Denk H. (1991). Modulation of alpha smooth muscle actin and desmin expression in perisinusoidal cells of normal and diseased human livers. Am J Pathol 138: 1233—1242.[Abstract]
• Schocklmann HO, Lang S., Sterzel B. (1999). Regulation of mesangial cell proliferation. Kidney Int 56: 1199—1207.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Sime PJ, Marr RA, Gauldie D., Xing Z., Hewlett BR, Graham FL, Gauldie J. (1998). Transfer of tumor necrosis factor- to rat lung induces severe pulmonary inflammation and patchy interstitial fibrogenesis with induction of transforming growth factor-β1 and myofibroblasts. Am J Pathol 153: 825—832.[Abstract/Free Full Text]
• Soo C., Hu FY, Zhang X., Wang Y., Beanes SR, Lorenz HP, Hedrick MH, Mackool RJ, Plaas A., Kim SJ, Longaker MT, Freymiller E., Ting K. ( 2000). Differential expression of fibromodulin, a transforming growth factor-β modulator, in fetal skin development and scarless repair. Am J Pathol 157: 423—433.[Abstract/Free Full Text]
• Surette ME, Fonteh AN, Bernatchez C., Chilton FH (1999). Perturbations in the control of cellular arachidoni c acid levels block cell growth and induce apoptosis in HL-60 cells. Carcinogenesis 20: 757—763.[Abstract/Free Full Text]
• Tamaki K., Okuda S., Ando T., Iwamoto T., Nakayama M., Fujishima M. (1994). TGF-β1 in glomerulosclerosi s and interstitial fibrosis of adriamycin nephropathy. Kidney Int 45: 525—536.[Web of Science][Medline] [Order article via Infotrieve]
• Tang WW, Ulich TR, Lacey DL, Hill DC, Qi M., Kaufman SA, Van GY, Tarpley JE, Yee JS (1996). Platelet-derived growth factor-BB induces renal tubulointerstitial myofibroblast formation and tubulointerstitial fibrosis. Am J Pathol 148: 1169—1180.[Abstract]
• Thrall RS, Vogel SN, Evans R., Shultz LD (1997). Role of tumor necrosis factor- in the spontaneous development of pulmonary fibrosis in viable motheaten mutant mice. Am J Pathol 151: 1303—1310.[Abstract]
• Tsujino K., Yamate J., Tsukamoto Y., Kumagai D., Kannan Y., Jippo T., Kuwamura M., Kotani T., Takeya M., Sakuma S. (1997). Establishment and characterization of cell lines derived from a transplantable rat malignant meningioma: Morphological heterogeneity and production of nerve growth factor. Acta Neuropathol 93: 461—470.[CrossRef][Medline] [Order article via Infotrieve]
• Valledor AF, Borras FE, Cullell-Young M., Celada A. (1998). Transcription factors that regulate monocyte/macrophage differentiation. J Leukoc Biol 63: 405—417.[Abstract]
• Vande Berg JS, Rudolph R., Poolman WL, Disharoon DR (1989). Comparative growth dynamics and actin concentration between cultured human myofibroblasts from granulating wounds and dermal fibroblasts from normal skin. Lab Invest 61: 532—538.[Web of Science][Medline] [Order article via Infotrieve]
• Van Goor H., Ding G., Kees-Folts D., Grond J., Schreiner GF, Diamond JR (1994). Macrophages and renal disease. Lab Invest 71: 456—464.[Web of Science][Medline] [Order article via Infotrieve]
• Xiao BG, Bai XF, Zhang GX, Link H. ( 1997). Transforming growth factor-β1 induces apoptosis of rat microglia without relation to bcl-2 oncoprotein expression. Neurosci Lett 226: 71—74.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Yamate J., Maeda M., Benn SJ, Laithwaite JE, Allan A., Ide M., Kuwamura M., Kotani T., Sakuma S., LaMarre J. (2001). Effects of lipopolysaccharide on a rat histiocytic sarcoma-derived cell line (HS-P) with macrophage-like nature. J Comp Pathol (in press).
• Yamate J., Maeda M., Tsukamoto Y., Benn SJ, Laithwaite JE, Allan A., Kannan Y., Ide M., Kuwamura M., Kotani T., Sakuma S., LaMarre J. (2001). Macrophage-like cell line (HS-P) from a rat histiocytic sarcoma. J Comp Pathol 124: 183—191.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Yamate J., Okado A., Kuwamura M., Tsukamoto Y., Ohashi F., Kiso Y., Nakatsuji S., Kotani T., Sakuma S., LaMarre J. (1998). Immunohistochemical analysis of macrophages, myofibroblasts, and transforming growth factor-β localization during rat renal interstitial fibrosis following long-term unilateral ureteral obstruction. Toxicol Pathol 26: 793— 801.[Abstract/Free Full Text]
• Yamate J., Tajima M., Shibuya K., Kuwamura M., Kotani T., Sakuma S. (1996). Phenotypic modulation in cisplatin-resistant cloned cells derived from transplantable rat malignant fibrous histiocytoma. Pathol Int 46: 557—567.[Web of Science][Medline] [Order article via Infotrieve]
• Yamate J., Tajima M., Shibuya K., Saitoh T. (1994). Enhancement of lipid phagocytosi s by cloned cells derived from rat malignant fibrous histiocytoma under hyperlipemic conditions. Pathol Int 44: 735—744.[Web of Science][Medline] [Order article via Infotrieve]
• Yamate J., Tajima M., Togo M., Shibuya K., Ihara M., Kudow S. (1991). Heterogeneity of cloned cell lines established from a transplantabl e rat malignant fibrous histiocytoma. Jpn J Cancer Res 82: 298—307.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Yamate J., Tsujino K., Kumagai D., Nakatsuji S., Kuwamura M., Kotani T., Sakuma S. (1997). Morphological characteristics of a transplantable histiocytic sarcoma (HS-J) in F344 rats and appearance of renal tubular hyaline droplets in HS-J-bearing rats. J Comp Pathol 116: 73—86.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]

Toxicologic Pathology, Vol. 29, No. 4, 483-491 (2001)
DOI: 10.1080/01926230152500103


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