Interplay of the inflammatory and stress systems in a hepatic cell line: Interactions between glucocorticoid receptor agonists and interleukin-6

Endocrinology

Volumn 151, Issue 11, 2010, Pages 5279-5293

  Visser, Koch ^a   Smith, Carine ^a   Louw, Ann ^a  

^a STELLENBOSCH UNIVERSITY   (South Africa)

Author keywords

[No Author keywords available]

Indexed keywords

AGENTS INTERACTING WITH TRANSMITTER, HORMONE OR DRUG RECEPTORS; AMYLOID A PROTEIN; C REACTIVE PROTEIN; DEXAMETHASONE; GAMMA GLUTAMYLTRANSFERASE; GLUCOCORTICOID RECEPTOR; GLUCOCORTICOID RECEPTOR AGONIST; INTERLEUKIN 6; PHOSPHOENOLPYRUVATE CARBOXYKINASE (ATP); TRANSCORTIN; TYROSINE AMINOTRANSFERASE; UNCLASSIFIED DRUG; GLUCOCORTICOID;

ANIMAL CELL; ARTICLE; DRUG PROTEIN BINDING; INFLAMMATION; LIVER CELL; LIVER CELL CARCINOMA; MOUSE; NONHUMAN; PRIORITY JOURNAL; STRESS; ANALYSIS OF VARIANCE; ANIMAL; CELL CULTURE; DRUG EFFECT; DRUG POTENTIATION; ENZYME LINKED IMMUNOSORBENT ASSAY; LIVER; METABOLISM; PHYSIOLOGICAL STRESS; PHYSIOLOGY; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; TUMOR CELL LINE; WESTERN BLOTTING;

ANALYSIS OF VARIANCE; ANIMALS; BLOTTING, WESTERN; CELL LINE, TUMOR; CELLS, CULTURED; DEXAMETHASONE; ENZYME-LINKED IMMUNOSORBENT ASSAY; GLUCOCORTICOIDS; INFLAMMATION; INTERLEUKIN-6; LIVER; MICE; RECEPTORS, GLUCOCORTICOID; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; STRESS, PHYSIOLOGICAL;

EID: 78049520101     PISSN: 00137227     EISSN: 00137227     Source Type: Journal    
DOI: 10.1210/en.2010-0368     Document Type: Article

References (91)

1. Tsigos C, Chrousos GP 2002 Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress. J Psychosom Res 53:865-871
2. Charmandari E, Tsigos C, Chrousos G 2005 Endocrinology of the stress response. Annu Rev Physiol 67:259-284
3. Newton R 2000 Molecular mechanisms of glucocorticoid action: what is important? Thorax 55:603-613
4. Ndubuisi MI, Patel K, Rayanade RJ, Mittelman A, May LT, Sehgal PB 1998 Distinct classes of chaperoned IL-6 in human blood: differential immunological and biological availability. J Immunol 160:494-501
5. May LT, Ndubuisi MI, Patel K, García D 1995 Interleukin-6 chaperones in blood. Ann NY Acad Sci 762:120-128
6. Mihrshahi R, Lewis JG, Ali SO 2006 Hormonal effects on the secretion and glycoform profile of corticosteroid-binding globulin. J Steroid Biochem Mol Biol 101:275-285
7. Duma D, Jewell CM, Cidlowski JA 2006 Multiple glucocorticoid receptor isoforms and mechanisms of post-translational modification. J Steroid Biochem Mol Biol 102:11-21
8. Beato M, Truss M, Chávez S 1996 Control of transcription by steroid hormones. Ann NY Acad Sci 784:93-123
9. De Bosscher K, Vanden Berghe W, Haegeman G 2003 The interplay between the glucocorticoid receptor and nuclear factor-kappaB or activator protein-1: molecular mechanisms for gene repression. Endocr Rev 24:488-522 (Pubitemid 37059110)
10. Arzt E 2001 Gp130 cytokine signaling in the pituitary gland: a paradigm for cytokine-neuro-endocrine pathways. J Clin Invest 108:1729-1733 (Pubitemid 34015115)
11. Heinrich PC, Behrmann I, Haan S, Hermanns HM, Müller-Newen G, Schaper F 2003 Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem J 374:1-20
12. Koj A 1996 Initiation of acute phase response and synthesis of cytokines. Biochim Biophys Acta 1317:84-94
13. Zhang Z, Jones S, Hagood JS, Fuentes NL, Fuller GM 1997 STAT3 acts as a co-activator of glucocorticoid receptor signaling. J Biol Chem 272:30607-30610
14. Turnbull AV, Rivier CL 1999 Regulation of the hypothalamic-pituitary- adrenal axis by cytokines: actions and mechanisms of action. Physiol Rev 79:1-71
15. Angeli A, Masera RG, Sartori ML, Fortunati N, Racca S, Dovio A, Staurenghi A, Frairia R 1999 Modulation by cytokines of glucocorticoid action. Ann NY Acad Sci 876:210-220
16. Knolle PA, Löser E, Protzer U, Duchmann R, Schmitt E, zum Büschenfelde KH, Rose-John S, Gerken G 1997 Regulation of endotoxin-induced IL-6 production in liver sinusoidal endothelial cells and Kupffer cells by IL-10. Clin Exp Immunol 107:555-561
17. Opherk C, Tronche F, Kellendonk C, Kohlmüller D, Schulze A, Schmid W, Schütz G 2004 Inactivation of the glucocorticoid receptor in hepatocytes leads to fasting hypoglycemia and ameliorates hyperglycemia in streptozotocin-induced diabetes mellitus. Mol Endocrinol 18:1346-1353
18. Bodwell JE, Kingsley LA, Hamilton JW 2004 Arsenic at very low concentrations alters glucocorticoid receptor (GR)-mediated gene activation but not GR-mediated gene repression: complex dose-response effects are closely correlated with levels of activated GR and require a functional GR DNA binding domain. Chem Res Toxicol 17:1064-1076
19. Miller MS, Buzard GS, McDowell AE 1993 In vivo inhibition of glucocorticoid-inducible gene expression by dimethylnitrosamine in rat liver. Biochem Pharmacol 45:1465-1470
20. Courtois A, Payen L, Guillouzo A, Fardel O 1999 Up-regulation of multidrug resistance-associated protein 2 (MRP2) expression in rat hepatocytes by dexamethasone. FEBS Lett 459:381-385
21. DuBois DC, Xu ZX, McKay L, Almon RR, Pyszcznski N, Jusko WJ 1995 Differential dynamics of receptor down-regulation and tyrosine aminotransferase induction following glucocorticoid treatment. J Steroid Biochem Mol Biol 54:237-243
22. Einstein M, Greenlee M, Rouen G, Sitlani A, Santoro J, Wang C, Pandit S, Mazur P, Smalera I, Weaver AP, Zeng YY, Ge L, Kelly T, Paiva T, Geissler W, Mosley RT, Williamson J, Ali A, Balkovec J, Harris G 2004 Selective glucocorticoid receptor nonsteroidal ligands completely antagonize the dexamethasone mediated induction of enzymes involved in gluconeogenesis and glutamine metabolism. J Steroid Biochem Mol Biol 92:345-356
23. Wang XL, Herzog B, Waltner-Law M, Hall RK, Shiota M, Granner DK 2004 The synergistic effect of dexamethasone and all-transretinoic acid on hepatic phosphoenolpyruvate carboxykinase gene expression involves the coactivator p300. J Biol Chem 279:34191-34200 (Pubitemid 39318042)
24. Hall RK, Wang XL, George L, Koch SR, Granner DK 2007 Insulin represses phosphoenolpyruvate carboxykinase gene transcription by causing the rapid disruption of an active transcription complex: a potential epigenetic effect. Mol Endocrinol 21:550-563 (Pubitemid 46188283)
25. Dewint P, Gossye V, De Bosscher K, Vanden Berghe W, Van Beneden K, Deforce D, Van Calenbergh S, Müller-Ladner U, Vander Cruyssen B, Verbruggen G, Haegeman G, Elewaut D 2008 A plant-derived ligand favoring monomeric glucocorticoid receptor conformation with impaired transactivation potential attenuates collagen-induced arthritis. J Immunol 180:2608-2615
26. Barouki R, Chobert MN, Billon MC, Finidori J, Tsapis R, Hanoune J 1982 Glucocorticoid hormones increase the activity of gamma-glutamyltransferase in a highly differentiated hepatoma cell line. Biochim Biophys Acta 721:11-21 (Pubitemid 13253868)
27. Chobert MN, Grondin G, Brouillet A, Laperche Y, Beaudoin AR 1996 Control of gamma-glutamyl transpeptidase expression by glucocorticoids in the rat pancreas. Correlation with granule formation. J Biol Chem 271:12431-12437 (Pubitemid 26160912)
28. Burgess SC, He T, Yan Z, Lindner J, Sherry AD, Malloy CR, Browning JD, Magnuson MA 2007 Cytosolic phosphoenolpyruvate carboxykinase does not solely control the rate of hepatic gluconeogenesis in the intact mouse liver. Cell Metab 5:313-320 (Pubitemid 46477858)
29. Smith C, Wilson NW, Louw A, Myburgh KH 2007 Illuminating the interrelated immune and endocrine adaptations after multiple exposures to short immobilization stress by in vivo blocking of IL-6. Am J Physiol Regul Integr Comp Physiol 292:R1439-R1447
30. Zvibel I, Brill S, Kariv R, Traister A, Golan T, Chebath J, Halpern Z, Revel M, Oren R 2004 Chimeric molecule IL-6/soluble IL-6 receptor is a potent mitogen for fetal hepatocytes. J Cell Physiol 200:245-252
31. Hill M, McCallum R 1991 Altered transcriptional regulation of phosphoenolpyruvate carboxykinase in rats following endotoxin treatment. J Clin Invest 88:811-816
32. Chichelnitskiy E, Vegiopoulos A, Berriel Diaz M, Ziegler A, Kleiman A, Rauch A, Tuckermann J, Herzig S 2009 In vivo phosphoenolpyruvate carboxykinase promoter mapping identifies disrupted hormonal synergism as a target of inflammation during sepsis in mice. Hepatology 50:1963-1971
33. Stojakovic T, Scharnagl H, Trauner M, Pieske B, Wellnitz B, Seelhorst U, Schilling D, Winkelmann BR, Boehm BO, März W 2010 Serum gamma-glutamyl transferase and mortality in persons undergoing coronary angiography-The Ludwigshafen Risk and Cardiovascular Health Study. Atherosclerosis 208:564-571
34. Coban S, Yildiz F, Terzi A, Al B, Ozgor D, Ara C, Polat A, Esrefoglu M 2010 The effect of caffeic acid phenethyl ester (CAPE) against cholestatic liver injury in rats. J Surg Res 159:674-679
35. Betts JC, Cheshire JK, Akira S, Kishimoto T, Woo P 1993 The role of NF-kappa B and NF-IL6 transactivating factors in the synergistic activation of human serum amyloid A gene expression by interleukin-1 and interleukin-6. J Biol Chem 268:25624-25631
36. Thorn CF, Whitehead AS 2002 Differential glucocorticoid enhancement of the cytokine-driven transcriptional activation of the human acute phase serum amyloid A genes, SAA1 and SAA2. J Immunol 169:399-406
37. Ganapathi MK, May LT, Schultz D, Brabenec A, Weinstein J, Sehgal PB, Kushner I 1988 Role of interleukin-6 in regulating synthesis of C-reactive protein and serum amyloid A in human hepatoma cell lines. Biochem Biophys Res Commun 157:271-277 (Pubitemid 19004856)
38. Zhang S, Liu Q, Wang J, Harnish DC 2009 Suppression of interleukin-6-induced C-reactive protein expression by FXR agonists. Biochem Biophys Res Commun 379:476-479
39. Emptoz-Bonneton A, Crave JC, LeJeune H, Brébant C, Pugeat M 1997 Corticosteroid-binding globulin synthesis regulation by cytokines and glucocorticoids in human hepatoblastoma-derived (HepG2) cells. J Clin Endocrinol Metab 82:3758-3762
40. Bartalena L, Hammond GL, Farsetti A, Flink IL, Robbins J 1993 Interleukin-6 inhibits corticosteroid-binding globulin synthesis by humanhepatoblastoma-derived (Hep G2) cells. Endocrinology 133:291-296
41. Smith CL, Hammond GL 1992 Hormonal regulation of corticosteroid-binding globulin biosynthesis in the male rat. Endocrinology 130:2245-2251
42. Castell JV, Gómez-Lechón MJ, David M, Hirano T, Kishimoto T, Heinrich PC 1988 Recombinant human interleukin-6 (IL-6/BSF-2/HSF) regulates the synthesis of acute phase proteins in human hepatocytes. FEBS Lett 232:347-350
43. Ganapathi MK, Rzewnicki D, Samols D, Jiang SL, Kushner I 1991 Effect of combinations of cytokines and hormones on synthesis of serum amyloid A and C-reactive protein in Hep 3B cells. J Immunol 147:1261-1265
44. Volanakis JE 2001 Human C-reactive protein: expression, structure, and function. Mol Immunol 38:189-197
45. Schäcke H, Döcke WD, Asadullah K 2002 Mechanisms involved in the side effects of glucocorticoids. Pharmacol Ther 96:23-43
46. Barnes PJ 2006 Corticosteroids: the drugs to beat. Eur J Pharmacol 533:2-14
47. Louw A, Swart P, de Kock SS, van der Merwe KJ 1997 Mechanism for the stabilization in vivo of the aziridine precursor 2-(4-acetoxyphenyl)- 2-chloro-N-methyl-ethylammonium chloride by serum proteins. Biochem Pharmacol 53:189-197
48. De Bosscher K, Vanden Berghe W, Beck IM, Van Molle W, Hennuyer N, Hapgood J, Libert C, Staels B, Louw A, Haegeman G 2005Afully dissociated compound of plant origin for inflammatory gene repression. Proc Natl Acad Sci USA 102:15827-15832
49. Zhang Z, Zhang ZY, Schluesener HJ 2009 Compound A, a plant origin ligand of glucocorticoid receptors, increases regulatory T cells and M2 macrophages to attenuate experimental autoimmune neuritis with reduced side effects. J Immunol 183:3081-3091
50. Gossye V, Elewaut D, Van Beneden K, Dewint P, Haegeman G, De Bosscher K 2010 A plant-derived glucocorticoid receptor modulator attenuates inflammation without provoking ligand-induced resistance. Ann Rheum Dis 69:291-296
51. Coghlan MJ, Jacobson PB, Lane B, Nakane M, Lin CW, Elmore SW, Kym PR, Luly JR, Carter GW, Turner R, Tyree CM, Hu J, Elgort M, Rosen J, Miner JN 2003 A novel antiinflammatory maintains glucocorticoid efficacy with reduced side effects. Mol Endocrinol 17:860-869
52. Schäcke H, Schottelius A, Döcke WD, Strehlke P, Jaroch S, Schmees N, Rehwinkel H, Hennekes H, Asadullah K 2004 Dissociation of transactivation from transrepression by a selective glucocorticoid receptor agonist leads to separation of therapeutic effects from side effects. Proc Natl Acad Sci USA 101:227-232 (Pubitemid 38084232)
53. Bamberger CM, Else T, Bamberger AM, Beil FU, Schulte HM 1999 Dissociative glucocorticoid activity of medroxyprogesterone acetate in normal human lymphocytes. J Clin Endocrinol Metab 84:4055-4061 (Pubitemid 30644194)
54. Bamberger CM, Schulte HM 2000 Molecular mechanisms of dissociative glucocorticoid activity. Eur J Clin Invest 30(Suppl 3):6-9
55. Vayssière BM, Dupont S, Choquart A, Petit F, Garcia T, Marchandeau C, Gronemeyer H, Resche-Rigon M 1997 Synthetic glucocorticoids that dissociate transactivation and AP-1 transrepression exhibit antiinflammatory activity in vivo. Mol Endocrinol 11:1245-1255 (Pubitemid 28041332)
56. Vanden Berghe W, Francesconi E, De Bosscher K, Resche-Rigon M, Haegeman G 1999 Dissociated glucocorticoids with anti-inflammatory potential repress interleukin-6 gene expression by a nuclear factor-kappaB-dependent mechanism. Mol Pharmacol 56:797-806 (Pubitemid 29491183)
57. Lin CW, Nakane M, Stashko M, Falls D, Kuk J, Miller L, Huang R, Tyree C, Miner JN, Rosen J, Kym PR, Coghlan MJ, Carter G, Lane BC 2002 trans-Activation and repression properties of the novel nonsteroid glucocorticoid receptor ligand 2,5-dihydro-9-hydroxy-10- methoxy-2,2,4-trimethyl-5-(1-methylcyclohexen-3-y1)- 1H-[1]benzopyrano[ 3,4-f]quinoline (A276575) and its four stereoisomers. Mol Pharmacol 62:297-303
58. Zhang JZ, Cavet ME, Vander Meid KR, Salvador-Silva M, López FJ, Ward KW 2009 BOL-303242-X, a novel selective glucocorticoid receptor agonist, with full anti-inflammatory properties in human ocular cells. Mol Vis 15:2606-2616
59. Robertson S, Allie-Reid F, Berghe WV, Visser K, Binder A, Africander D, Vismer M, De Bosscher K, Hapgood J, Haegeman G, Louw A 2010 Abrogation of glucocorticoid receptor dimerization correlates with dissociated glucocorticoid behavior of compound A. J Biol Chem 285:8061-8075
60. Bradford MM 1976 A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248-254
61. Diamondstone TI 1966 Assay of tyrosine transaminase activity by conversion of p-hydroxyphenylpyruvate to p-hydroxybenzaldehyde. Anal Biochem 16:395-401
62. Chang HC, Lane MD 1966 The enzymatic carboxylation of phosphoenolpyruvate. II. Purification and properties of liver mitochondrial phosphoenolpyruvate carboxykinase. J Biol Chem 241:2413-2420
63. Lipmann F, Tuttle LC 1945 A specific micromethod for the determination of acyl phosphates. J Biol Chem 159:21-28
64. Engelbrecht Y, de Wet H, Horsch K, Langeveldt CR, Hough FS, Hulley PA 2003 Glucocorticoids induce rapid up-regulation of mitogen-activated protein kinase phosphatase-1 and dephosphorylation of extracellular signal-regulated kinase and impair proliferation in human and mouse osteoblast cell lines. Endocrinology 144:412-422
65. Wüst S, Tischner D, John M, Tuckermann JP, Menzfeld C, Hanisch UK, van den Brandt J, Lühder F, Reichardt HM 2009 Therapeutic and adverse effects of a non-steroidal glucocorticoid receptor ligand in a mouse model of multiple sclerosis. PLoS One 4:e8202
66. Beck IM, Vanden Berghe W, Vermeulen L, Yamamoto KR, Haegeman G, De Bosscher K 2009 Crosstalk in inflammation: the interplay of glucocorticoid receptor-based mechanisms and kinases and phosphatases. Endocr Rev 30:830-882
67. Oakley RH, Cidlowski JA 1993 Homologous down regulation of the glucocorticoid receptor: the molecular machinery. Crit Rev Eukaryot Gene Expr 3:63-88
68. Kirwan J, Power L 2007 Glucocorticoids: action and new therapeutic insights in rheumatoid arthritis. Curr Opin Rheumatol 19:233-237
69. Adcock IM, Barnes PJ 2008 Molecular mechanisms of corticosteroid resistance. Chest 134:394-401
70. Louw A, Swart P 1999 Salsola tuberculatiformis Botschantzev and an aziridine precursor analog mediate the in vivo increase in free corticosterone and decrease in corticosteroid-binding globulin in female Wistar rats. Endocrinology 140:2044-2053
71. Hirasawa H, Oda S, Nakamura M 2009 Blood glucose control in patients with severe sepsis and septic shock. World J Gastroenterol 15:4132-4136
72. Szrama J, Smuszkiewicz P, Trojanowska I 2009 Glycemic profile and effectiveness and safety of insulin therapy in septic patients: is the blood glucose level sufficient? Pol Arch Med Wewn 119:621-627
73. Borghetti P, Saleri R, Mocchegiani E, Corradi A, Martelli P 2009 Infection, immunity and the neuroendocrine response. Vet Immunol Immunopathol 130:141-162
74. Chrousos GP, Gold PW 1992 The concepts of stress and stress system disorders. Overview of physical and behavioral homeostasis. JAMA 267:1244-1252
75. Selye H 1998 A syndrome produced by diverse nocuous agents. 1936. J Neuropsychiatry Clin Neurosci 10:230-231
76. Thorn CF, Lu ZY, Whitehead AS 2003 Tissue-specific regulation of the human acute-phase serum amyloid A genes, SAA1 and SAA2, by glucocorticoids in hepatic and epithelial cells. Eur J Immunol 33:2630-2639
77. Thorn CF, Lu ZY, Whitehead AS 2004 Regulation of the human acute phase serum amyloid A genes by tumour necrosis factor-alpha, interleukin-6 and glucocorticoids in hepatic and epithelial cell lines. Scand J Immunol 59:152-158
78. Foyn Bruun C, Sletten K, Marhaug G 1998 Mouse serum amyloid A(SAA) proteins isolated by two-dimensional electrophoresis: characterization of isotypes and the effect of separate and combined administrations of cytokines, dexamethasone and lipopolysaccharide (LPS) on serum levels and isotype distribution. Clin Exp Immunol 111:231-236
79. Ochrietor JD, Harrison KA, Zahedi K, Mortensen RF 2000 Role of STAT3 and C/EBP in cytokine-dependent expression of the mouse serum amyloid P-component (SAP) and C-reactive protein (CRP) genes. Cytokine 12:888-899 (Pubitemid 30479470)
80. Ku NO, Mortensen RF 1993 The mouse C-reactive protein (CRP) gene is expressed in response to IL-1 but not IL-6. Cytokine 5:319-326
81. Gossye V, Elewaut D, Bougarne N, Bracke D, Van Calenbergh S, Haegeman G, De Bosscher K 2009 Differential mechanism of NF-kappaB inhibition by two glucocorticoid receptor modulators in rheumatoid arthritis synovial fibroblasts. Arthritis Rheum 60:3241-3250
82. van Loo G, Sze M, Bougarne N, Praet J, Mc Guire C, Ullrich A, Haegeman G, Prinz M, Beyaert R, De Bosscher K 2010 Antiinflammatory properties of a plant-derived nonsteroidal, dissociated glucocorticoid receptor modulator in experimental autoimmune encephalomyelitis. Mol Endocrinol 24:310-322
83. Reichardt HM, Tuckermann JP, Göttlicher M, Vujic M, Weih F, Angel P, Herrlich P, Schütz G 2001 Repression of inflammatory responses in the absence of DNA binding by the glucocorticoid receptor. EMBO J 20:7168-7173
84. Schuett H, Luchtefeld M, Grothusen C, Grote K, Schieffer B 2009 How much is too much? Interleukin-6 and its signalling in atherosclerosis. Thromb Haemost 102:215-222
85. Johansson-Haque K, Palanichamy E, Okret S 2008 Stimulation of MAPK-phosphatase 1 gene expression by glucocorticoids occurs through a tethering mechanism involving C/EBP. J Mol Endocrinol 41:239-249
86. Necela BM, Cidlowski JA 2004 Mechanisms of glucocorticoid receptor action in noninflammatory and inflammatory cells. Proc Am Thorac Soc 1:239-246
87. Liden J, Rafter I, Truss M, Gustafsson JA, Okret S 2000 Glucocorticoid effects on NF-kappaB binding in the transcription of the ICAM-1 gene. Biochem Biophys Res Commun 273:1008-1014
88. Short MK, Clouthier DE, Schaefer IM, Hammer RE, Magnuson MA, Beale EG 1992 Tissue-specific, developmental, hormonal, and dietary regulation of rat phosphoenolpyruvate carboxykinase-human growth hormone fusion genes in transgenic mice. Mol Cell Biol 12:1007-1020
89. Burnstein KL, Jewell CM, Cidlowski JA 1990 Human glucocorticoid receptor cDNA contains sequences sufficient for receptor down-regulation. J Biol Chem 265:7284-7291
90. Geng CD, Schwartz JR, Vedeckis WV 2008 A conserved molecular mechanism is responsible for the auto-up-regulation of glucocorticoid receptor gene promoters. Mol Endocrinol 22:2624-2642
91. Geng CD, Vedeckis WV 2005 c-Myb and members of the c-Ets family of transcription factors act as molecular switches to mediate opposite steroid regulation of the human glucocorticoid receptor1A promoter. J Biol Chem 280:43264-43271