Abstract
The hyperthermia-induced activation of the stress protein response allows cells to withstand metabolic insults that would otherwise be lethal. This phenomenon is referred to as thermotolerance. Heat shock protein 70 (HSP70) has been shown to play an important role in this hyperthermia-related cell protection. HSP70 confers protection against cellular and tissue injury. Our objective was to determine the effect of heat stress on the histopathology of pulmonary fibrosis caused by the administration of lipopolysaccharide (LPS) in Wistar rats. The rats were randomly divided into three groups. In the control group, rats were heated to 42°C for 15 min. In the LPS group, rats were given LPS in 0.9% NaCl solution (10 mg/kg body weight). In the WH (whole-body hyperthermia) +LPS group, rats were heated to 42°C for 15 min, and 48 h later they were injected with LPS dissolved in a 0.9% NaCl solution (10 mg/kg body weight). We investigated lung histopathology and performed a Northern blot analysis daily. Hyperthermia was shown to reduce tissue injury caused by the administration of LPS. Pulmonary tissue HSP70 mRNA was found to be elevated at 3 h after heating. HSP70 protein levels in the serum increased after whole-body hyperthermia. However, neither the expression of HSP47 mRNA nor the expression of type I or type III collagen mRNA was induced by the administration of LPS after whole-body hyperthermia. These data indicate that thermal pretreatment is associated with the induction of HSP70 protein synthesis, which subsequently attenuates tissue damage in experimental lung fibrosis.
Similar content being viewed by others
References
Pespeni M, Hodnett M, Pittet JF (2005) In vivo stress preconditioning. Methods 35:158–164
Kregel KC (2002) Heat shock proteins: modifying factors in physiological stress responses and acquired thermotolerance. J Appl Physiol 92:2177–2186
Mayer MP, Bukau B (2005) Hsp70 chaperones: cellular functions and molecular mechanism. Cell Mol Life Sci 62:670–684
Schlesinger MJ (1990) Heat shock proteins. J Biol Chem 265:12111–12114
Welch WJ (1992) Mammalian stress response: cell physiology, structure/function of stress proteins, and implications for medicine and disease. Physiol Rev 72:1063–1081
Hudson LD, Hough CL (2006) Therapy for late-phase acute respiratory distress syndrome. Clin Chest Med. 27:671–677
Adamson IY, Young L, Bowden DH (1988) Relationship of alveolar epithelial injury and repair to the induction of pulmonary fibrosis. Am J Pathol 130:377–383
Pan T, Mason RJ, Westcott JY, Shannon JM (2001) Rat alveolar type II cells inhibit lung fibroblast proliferation in vitro. Am J Respir Cell Mol Biol 25:353–361
Shimabukuro DW, Sawa T, Gropper MA (2003) Injury and repair in lung and airways. Crit Care Med 31:524–531
Neff TA, Stocker R, Frey HR, Stein S, Russi EW (2003) Long-term assessment of lung function in survivors of severe ARDS. Chest 123:845–853
Ashcroft T, Simpson JM, Timbrell V (1988) Simple method of estimating severity of pulmonary fibrosis on a numerical scale. J Clin Pathol 41:467–470
Chua F, Gauldie J, Laurent GJ (2005) Pulmonary fibrosis: searching for model answers. Am J Respir Cell Mol Biol 33:9–13
Nagata K, Saga S, Yamada KM (1988) Characterization of a novel transformation-sensitive heat-shock protein (HSP47) that binds to collagen. Biochem Biophys Res Commun 153:428–434
Nakai A, Satoh M, Hirayoshi K, Nagata K (1992) Involvement of the stress protein HSP47 in procollagen processing in the endoplasmic reticulum. J Cell Biol 117:903–914
Satoh M, Hirayoshi K, Yokota S, Hosokawa N, Nagata K (1996) Intracellular interaction of collagen-specific stress protein HSP47 with newly synthesized procollagen. J Cell Biol 133:469–483
Razzaque MS, Taguchi T (1999) The possible role of colligin/HSP47, a collagen-binding protein, in the pathogenesis of human and experimental fibrotic diseases. Histol Histopathol 14:1199–1212
Hagiwara S, Iwasaka H, Matsumoto S, Noguchi T, Yoshioka H (2007) Coexpression of HSP47 gene and type I and type III collagen genes in LPS-induced pulmonary fibrosis in rats. Lung 185:31–37
Craig EA (1985) The heat shock response. Crit Rev Biochem 18:239–280
Subjeck JR, Shyy TT (1986) Stress protein systems of Mammalian cells. Am J Physol 250:1–17
Lindquist S (1986) The heat shock response. Annu Res Biochem 55:1151–1191
Kiang JG, Tsokos GC (1998) Heat shock protein 70 kDa: molecular biology, biochemistry, and physiology. Pharmacol Ther 80:183–201
Alexandrova M, Farkas P (1992) Stress-induced changes of glucocorticoid receptor in rat liver. J Steroid Biochem 42:493–498
Gathiram P, Wells MT, Brock-Utne JG, Gaffin SL (1988) Prophylactic corticosteroid increased survival in experimental heat stroke in primates. Aviat Space Eviron Med 59:352–355
Carter EA, Gonnella A, Tompkins RG (1992) Increased transcellular permeability of rat small intestine after thermal injury. Burns 18:117–120
Hass MA, Massaro D (1988) Regulation of synthesis of superoxide dismutase in rat lung during oxidant and hyperthermic stresses. J Biol Chem 263:776–781
Johnston RJ, Kucey BL (1988) Competitive inhibition of HSP70 gene expression causes thermosensitivity. Science 242:1551–1554
Riabowol KT, Mizzen LA, Welch WJ (1988) Heat shock is lethal to fibroblasts microinjected with antibodies against HSP70. Science 242:433–436
Beckman RP, Mizzen LA, Welch WJ (1990) Interaction of HSP70 with newly synthesized proteins. Science 248:850–854
Kazuhiro N (1996) HSP47: a collagen-specific molecular chaperone. Trends Biochem Sci 21:21–26
Kazuhiro N (1998) Expression and function of heat shock protein 47; a collagen-specific molecular chaperone in the endoplasmic reticulum. Matrix Biol 16:379–386
Kudo H, Hirayoshi K, Kitagawa Y, Imamura S, Nagata K (1994) Two collagen-binding proteins, osteonectin and HSP47, are coordinately induced in transformed keratinocytes by heat and other stresses. Exp Cell Res 212: 219–224
Lele Z, Engel S, Krone PH (1997) Hsp47 and hsp70 gene expression is differentially regulated in a stress- and tissue-specific manner in zebrafish embryos. Dev Genet 21:123–133
Shibolet S, Lancaster MC, Danon Y (1976) Heat stroke: a review. Aviat Space Environ Med 47:285–301
Styrt B, Sugarman B (1990) Antipyresis and fever. Arch Intern Med 150:1589–1597
Acknowledgments
The authors thank Professor K. Nagata (Kyoto University, Japan) for the plasmid with the HSP47 mRNA insert, which enabled us to perform the Northern hybridization analysis.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Hagiwara, S., Iwasaka, H., Matsumoto, S. et al. Association Between Heat Stress Protein 70 Induction and Decreased Pulmonary Fibrosis in an Animal Model of Acute Lung Injury. Lung 185, 287–293 (2007). https://doi.org/10.1007/s00408-007-9018-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00408-007-9018-x