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Influx of macrophages into livers of rats treated with hepatotoxicants (thioacetamide, allyl alcohol, d-galactosamine) induces expression of HSP25

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Abstract

Treatment of rats with a single dose of thioacetamide (TAA) provokes centrilobular inflammation and a significant expression of heat shock protein HSP25 in hepatocytes surrounding the area of inflammation. The HSP25 accumulation in hepatocytes adjacent to inflammatory regions was confirmed by identification of positive hepatocytes concentrated at periportal areas after treatment of rats with allyl alcohol (AA) or distributed diffusely throughout liver lobule after treatment with d-galactosamine (d-gal). In our model of TAA-treated rats the use of the anti-inflammatory drug—indomethacin, and the redox-regulating drug—N-acethylcysteine (NAC), significantly attenuated TAA-induced HSP25 expression and evoked morphological changes of recruited ED1+ macrophages. Treatment of rats with gadolinium chloride (GdCl3) decreased considerably the number of Kupffer cells (ED2+ macrophages) without affecting significantly the number and morphology of ED1+ macrophages as well as the expression pattern of TAA-induced HSP25. Our data shows for the first time that ED1+ macrophages recruited into the liver by treatment with TAA play a significant role in HSP25 induction in hepatocytes.

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References

  • Aliprantis AO, Diez-Roux G, Mulder LCF, Zychlinsky A, Lang RA (1996) Do macrophages kill through apoptosis? Immunol Today 17:573–576

    Article  PubMed  CAS  Google Scholar 

  • Andrés D, Sánchez-Reus I, Bautista M, Cascales M (2003) Depletion of Kupffer cell function by gadolinium chloride attenuates thioacetamide-induced hepatotixicity expression of metalothionein and HSP70. Biochem Pharmacol 66:917–926

    Article  PubMed  CAS  Google Scholar 

  • Arrigo A-P, Paul C, Ducasse C, Manero F, Kretz-Remy C, Virot S, Javouhey E, Mounier N, Diaz-Latoud C (2002) Small stress proteins: novel negative modulators of apoptosis induced independently of reactive oxygen species. In: ArrigoA-P, Müller WEG (ed) Small stress proteins. Prog Mol Subcell Biol, vol 28. Springer-Verlag Berlin Heidelberg, pp 185–204

  • Bachmann MF, Kundig TM (2005) Immune defense, cell mediated. In: Meyers RA (ed) Encyclopedia of molecular cell biology and molecular medicine, vol 6, Wiley VCH Verlag GmbH & Co. KGaA, Weinheim, pp 339–358

  • Berra A, Dutt JE, Nouri M, Foster CS (1994) Heat shock protein expression in human conjunctiva. Invest Ophthalmol Vis Sci 35:352–357

    PubMed  CAS  Google Scholar 

  • Bour ES, Ward LK, Cornman GA, Isom HC (1996) Tumor necrosis factor-induced apoptosis in hepatocytes in long-term culture. Am J Pathol 148:485–495

    PubMed  CAS  Google Scholar 

  • Ciocca DR, Vargas-Roig LM (2002) Hsp27 as a prognostic and predictive factor in cancer In: ArrigoA-P, Müller WEG (eds) Small stress proteins. Prog Mol Subcell Biol, vol 28. Springer-Verlag Berlin Heidelberg, pp 205–218

  • Ciocca DR, Rozados VR, Cuello Carrion FD, Gervasoni SI, Matar P, Scharovsky OG (2003) Hsp25 and Hsp70 in rodent tumors treated with doxorubicin and lovastatin. Cell Stress Chaperones 8:26–36

    Article  PubMed  CAS  Google Scholar 

  • Damoiseaux JGMC, Dopp EA, Calame W, Chao D, MacPherson GG, Dijkstra CD (1994) Rat macrophages lysosomal membrane antigen recognised by monoclonal antibody ED1. Immunol 83:140–147

    CAS  Google Scholar 

  • De AK, Kodys KM, Yeh BS, Miller-Graziano C (2000) Exaggerated human monocyte IL-10 concomitant to minimal TNF-α induction by heat shock protein 27 (Hsp27) suggests Hsp27 is primarily an anti-inflammatory stimulus. J Immunol 165:3951–3958

    PubMed  CAS  Google Scholar 

  • Duffield JS (2003) The inflammatory macrophage: a story of Jekyll and Hyde. Clin Sci 104:27–38

    Article  PubMed  CAS  Google Scholar 

  • Ethridge RT, Ehlers RA, Hellmich MR, Rajaraman S, Evers BM (2000) Acute pancreatitis results in induction of heat shock proteins 70 and 27 and heat shock factor-1. Pancreas 21:248–256

    Article  PubMed  CAS  Google Scholar 

  • Garrido C, Ottavi P, Fromentin A, Hammann A, Arrigo AP, Chauffert B, Mehlen P (1997) HSP27 as a mediator of confluence-dependent resistance to cell death induced by anticancer drugs. Cancer Res 57:2661–2667

    PubMed  CAS  Google Scholar 

  • Gorman AM, Szegezdi E, Quigney DJ, Samali A (2005) Hsp27 inhibits 6-hydroxydopamine-induced cytochrome c release and apoptosis in PC12 cells. Biochem Biophys Res Commun 327:801–810

    Article  PubMed  CAS  Google Scholar 

  • Gordon S (2003) Alternative activation of macrophages. Nat Rev Immunol 3: 23–35

    Article  PubMed  CAS  Google Scholar 

  • Gosset P, Wallaert B, Tonnel AB, Fourneau C (1999) Thiol regulation of the production of TNF-alpha, IL-6 and IL-8 by human alveolar macrophages. Eur Respir J 14:98–105

    Article  PubMed  CAS  Google Scholar 

  • Han DW (2002) Intestinal endotoxemia as a pathogenetic mechanism in liver failure. World J Gastroenterol 8:961–965

    PubMed  Google Scholar 

  • Hardonk MJ, Dijkhuis FWJ, Hulstaert CE (1992) Heterogeneity of rat liver and spleen macrophages in gadolinium chloride-induced elimination and repopulation. J Leucoc Biol 52: 296–302

    CAS  Google Scholar 

  • Hastie AT, Everts KB, Zangrilli J, Shaver JR, Pollice MB, Fish JE, Peters SP (1997) HSP27 elevated in mild allergic inflammation protects airway epithelium from H2SO4 effects. Am J Physiol 273:L401–L409

    PubMed  CAS  Google Scholar 

  • Hulten LM, Lindmark H, Schersten H, Wiklund O, Nilsson FN, Riise GC (1998) Butylated hydroxytoluene and N-acetylcysteine attenuates tumor necrosis factor-alpha (TNF-alpha) secretion and TNF-alpha mRNA expression in alveolar macrophages from human lung transplant recipients in vitro. Transplantation 66:364–369

    Article  PubMed  CAS  Google Scholar 

  • Ide M, Kuwamura M, Kotani T, Sawamoto O, Yamate J (2005) Effects of gadolinium chloride (GdCl(3)) on the appearance of macrophage populations and fibrogenesis in thioacetamide-induced rat hepatic lesions. J Comp Pathol 133:92–102

    Article  PubMed  CAS  Google Scholar 

  • Jacobson MD (1996) Reactive oxygen species and programmed cell death. Trends Biochem Sci 21:83–86

    Article  PubMed  CAS  Google Scholar 

  • Jäättelä M (1994) Over-expression of hsp70 confers tumorigenicity to mouse fibrosarcoma cells. Int J Cancer 60:689–693

    Google Scholar 

  • Johnson CD, Kudsk KA (1999) Nutrition and intestinal mucosal immunity. Clin Nutr 18:337–344

    Article  PubMed  CAS  Google Scholar 

  • Kono H, Fujii H Asakawa M, Yamamoto M, Maki A, Matsuda M, Rusyn I, Matsumoto Y (2002) Functional heterogeneity of Kupffer cell population is involved in the mechanism of Gadolinium Chloride in Rats administrated endotoxin. J Surg Res 106:179–187

    Article  PubMed  CAS  Google Scholar 

  • Kono H, Fujii H, Amemiya H, Asakawa M, Hirai Y, Maki A, Tsuchiya M, Matsuda M, Yamamoto M (2005) Role of Kupffer cells in lung injury in rats administered endotoxin 1. J Surg Res 129:176–189

    Article  PubMed  CAS  Google Scholar 

  • Kudsk KA (2002) Current aspects of mucosal immunology and its influence by nutrition. Am J Surg 183:390–398

    Article  PubMed  Google Scholar 

  • Laskin DL, Laskin JD (2001) Role of macrophages and inflammatory mediators in chemically induced toxicity. Toxicology 160:111–118

    Article  PubMed  CAS  Google Scholar 

  • Lee YJ, Lee DH, Cho CK, Bae S, Jhon GJ, Lee SJ, Soh JW, Lee YS (2005a) HSP25 inhibits protein kinase C delta-mediated cell death through direct interaction. J Biol Chem 280:18108–18119

    Article  CAS  Google Scholar 

  • Lee YJ, Lee DH, Cho CK, Chung HY, Bae S, Jhon GJ, Soh JW, Jeoung DI, Lee SJ, Lee YS (2005b) HSP25 inhibits radiation-induced apoptosis through reduction of PKCdelta-mediated ROS production. Oncogene 24:3715–3725

    Article  CAS  Google Scholar 

  • Leonardi R, Villari L, Caltabiano M, Travali S (2001) Heat shock protein 27 expression in the epithelium of periapical lesions. J Endod 27:89–92

    Article  PubMed  CAS  Google Scholar 

  • Lindeman B, Skarpen E, Huitfeldt HS (1998) Stress protein expression in rat liver during tumour promotion: induction of heat-shock protein 27 in hepatocytes exposed to 2-acetylaminofluorene. Carcinogenesis 19:1559–1563

    Article  PubMed  CAS  Google Scholar 

  • Löw-Friedrich I, Weisensee D, Mitrou P, Schoeppe W (1992) Cytokines induce stress protein formation in cultured cardiac myocytes. Basic Res Cardiol 87:12–18

    Article  PubMed  Google Scholar 

  • Mehlen P, Preville X, Chareyron P, Briolay J, Klemenz R, Arrigo A-P (1995) Constitutive expression of human hsp27, Drosophila hsp27 or human alpha B-crystallin confers resistance to TNF-and oxidative stress-induced cytotoxicity in stably transfected murine L929 fibroblasts. J Immunol 154:363–374

    PubMed  CAS  Google Scholar 

  • Morimoto RI, Tissières A, Georgopoulos C (1990) Stress proteins in biology and medicine. In: Morimoto RI, Tissières A, Georgopoulos C (eds) Stress proteins in biology and medicine. Cold Spring Harbor Press, New York pp 1–36

    Google Scholar 

  • Moseley PL (1998) Heat shock proteins and the inflammatory response. Ann N Y Acad Sci 851: 206–213

    Article  Google Scholar 

  • Mosher B, Dean R, Harkema J, Remick D, Palma J, Crockett E (2001) Inhibition of Kupffer cells. Reduced CXC chemokine production and liver injury. J Surg Res 99: 201–210

    Article  PubMed  CAS  Google Scholar 

  • Park KM, Kramers K, Vayssier-Taussat M, Chen A, Bonventre JV (2002) Prevention of kidney ischemia/reperfusion-induced functional injury, MAPK and MAPK kinase activation, and inflammation by remote transient ureteral obstruction. J Biol Chem 277:2040–2049

    Article  PubMed  CAS  Google Scholar 

  • Petersen BE, Zajac VF, Michalopoulos GK (1998) Hepatic oval cell activation in response to injury following chemically induced periportal or pericentral damage in rats. Hepatology 27:1030–1038

    Article  PubMed  CAS  Google Scholar 

  • Polla BS, Bachelet M, Elia G, Santoro G (1998) Stress proteins and inflammation. Ann N Y Acad Sci 851:75–85

    Article  PubMed  CAS  Google Scholar 

  • Porcheray F, Viaud S, Rimaniol AC, Leone C, Samah B, Dereuddre-Bosquet N, Dormont D, Gras G (2005) Macrophage activation switching: an asset for the resolution of inflammation. Clin Exp Immunol 142:481–489

    PubMed  CAS  Google Scholar 

  • Salminen WF, Roberts SM, Fenna M, Voellmy R (1997) Heat shock protein induction in murine liver after acute treatment with cocaine. Hepatology 25:1147–1153

    Article  PubMed  CAS  Google Scholar 

  • Salminen WF Jr, Voellmy R, Roberts SM (1998). Effect of N-acetylcysteine on heat shock protein induction by acetaminophen in mouse liver. J Pharmacol Exp Ther 286:519–524

    PubMed  CAS  Google Scholar 

  • Victor VM, Guayerbas N, Garrote D, Del Rio M, De la Fuente M (1999) Modulation of murine macrophage function by N-acetylcysteine in a model of endotoxic shock. Biofactors 10:347–357

    PubMed  CAS  Google Scholar 

  • Wang G, Klostergaard J, Khodadadian M, Wu J, Wu T-W, Fung KP, Carper SW, Tomasovic SP (1996) Murine cells transfected with human Hsp27 cDNA resist TNF-induced cytotoxicity. J Immunother Emphasis Tumor Immunol 19:9–20

    PubMed  CAS  Google Scholar 

  • Whiteland JL, Nicholls SM, Shimeld C, Easty DL, Wiliams NA, Hill TJ (1995) Immunohistochemical detection of T-cell subsets and Rother leucocytes in parafin-embedded rat and Mouse tissues with monoclonal antibodies. J Histochem Cytochem 43:313–320

    PubMed  CAS  Google Scholar 

  • Yamada T, Takahashi S, Masuda K, Ohara H, Nakazawa T, Sano H, Ando T, Nakamura S, Kobayashi S, Kuno A, Aoki S, Nomura T, Joh T, Itoh M (2003) Kupffer-cell depletion attenuates colonic and extracolonic granulomatous inflammation in chronic colitis. J Lab Clin Med 142:268–277

    Article  PubMed  CAS  Google Scholar 

  • Zborek A, Malusecka E, Krzyzowska-Gruca S, Wysocka A, Krawczyk Z (2002) Immunohistochemical studies on the expression pattern of molecular chaperones HSC70 and HSP25 and cell cycle-related proteins cyclin D1 and PCNA in rat liver after thioacetamide intoxication. Histochem Cell Biol 118:311–319

    PubMed  CAS  Google Scholar 

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Acknowledgements

This work was supported by the grant awarded to ZK by the Foundation for Polish Science. We thank Ms A. Kyrcz and Ms I. Peick for their excellent technical assistance.

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Zborek, A., Malusecka, E., Rusin, A. et al. Influx of macrophages into livers of rats treated with hepatotoxicants (thioacetamide, allyl alcohol, d-galactosamine) induces expression of HSP25. J Mol Hist 37, 381–389 (2006). https://doi.org/10.1007/s10735-006-9068-z

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