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Hepatic Thrombopoietin MRNA Is Increased in Acute Inflammation
Hepatic Thrombopoietin MRNA Is Increased in Acute Inflammation
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Thromb Haemost 2001; 86: 1421–4
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Wolber et al.: Increased TPO mRNA in Inflammation
tions, but furthermore reacts to systemic inflammation with increased 2. Sungaran R, Markovic B, Chong BH. Localization and regulation of throm-
TPO mRNA expression. bopoietin mRNA expression in human kidney, liver, bone marrow, and
Because TPO mRNA levels rise in HepG2 cells on IL-6 treatment spleen using in situ hybridization. Blood 1997; 89: 101-7.
and the promoter sequences flanking the TPO gene contain 13 putative 3. Gurney AL, Kuang WJ, Xie MH, Malloy BE, Eaton DL, de Sauvage FJ.
Genomic structure, chromosomal localization, and conserved alternative
IL-6 response elements (CTGGGA) (10), TPO can be considered an
splice forms of thrombopoietin. Blood 1995; 85: 981-8.
acute phase protein. Folman et al. (11) have pointed out that increases
4. Nagata Y, Shozaki Y, Nagahisa H, Nagasawa T, Abe T, Todokoro K.
in both gene expression and mRNA stability could be responsible for Serum thrombopoietin level is not regulated by transcription but by the
TPO mRNA accumulation in response to IL-6. Irrespective of the total counts of both megakaryocytes and platelets during thrombocytopenia
molecular mechanisms controlling TPO mRNA levels, excess of TPO and thrombocytosis. Thromb Haemost 1997; 77: 808-14.
and the resulting reactive thrombocytosis appear to be part of the acute 5. Fielder PJ, Gurney AL, Stefanich E, Marian M, Moore MW, Carver-
phase response. This notion is supported by data showing that concen- Moore K, de Sauvage FJ. Regulation of thrombopoietin levels by
trations of circulating IL-6 are elevated in reactive thrombocytosis (8) c-mpl-mediated binding to platelets. Blood 1996; 87: 2154-61.
and correlated with the concentration of TPO (9). The alterations of the 6. Kuter DJ, Rosenberg RD. The reciprocal relationship of thrombopoietin
level of circulating TPO in response to inflammation resemble those of (c-Mpl ligand) to changes in the platelet mass during busulfan-induced
acute phase reactants like IL-6 and C-reactive protein (24). It has been thrombocytopenia in the rabbit. Blood 1995; 85: 2720-30.
earlier demonstrated that LPS induces IL-6 mRNA expression in many 7. Cerutti A, Custodi P, Duranti M, Noris P, Balduini CL. Thrombopoietin
organs and a rise in circulating IL-6 protein peaking 1 to 2 h after a levels in patients with primary and reactive thrombocytosis. Br J Haematol
1997; 99: 281-4.
single intravenous injection (25).
8. Heits F, Katschinski DM, Wilmsen U, Wiedemann GJ, Jelkmann W. Serum
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Thromb Haemost 2001; 86: 1421–4
22. Ishikawa T, Ichida T, Matsuda Y, Sugitani S, Sugiyama M, Kato T, tor p75 fusion protein (TNFR:Fc) alters endotoxin-induced activation of the
Miyazaki H, Asakura H. Expression of hepatic thrombopoietin mRNA in kinin, fibrinolytic, and coagulation systems in normal humans. Thromb
primary cultured hepatocytes and in rats with acute liver injury or bone Haemost 1998; 80: 114-8.
marrow suppression with or without cirhosis. J Gastroenterol Hepatol 2000; 28. Yeaman MR. The role of platelets in antimicrobial host defense. Clin Infect
15: 647-53. Dis 1997; 25: 951-68.
23. Qian S, Fu F, Li W, Chen Q, de Sauvage FJ. Primary role of the liver in 29. Henn V, Slupsky JR, Grafe M, Anagnostopoulos I, Forster R, Müller-
thrombopoietin production shown by tissue-specific knockout. Blood 1998; Berghaus G, Kroczek RA. CD40 ligand on activated platelets triggers an
92: 2189-91. inflammatory reaction of endothelial cells. Nature 1998; 391: 591-4.
24. Cerutti A, Custodi P, Duranti M, Cazzola M, Balduini CL. Circulating 30. Oda A, Miyakawa Y, Druker BJ, Ozaki K, Ohashi H, Kato T, Miyazaki H,
thrombopoietin in reactive conditions behaves like an acute phase reactant. Handa M, Ikebuchi K, Ikeda Y. Thrombopoietin-induced signal trans-
Clin Lab Haematol 1999; 21: 271-5. duction and potentiation of platelet activation. Thromb Haemost 1999; 82:
25. Ulich TR, Guo KZ, Remick D, del Castillo J, Yin SM. Endotoxin-induced 377-84.
cytokine gene expression in vivo. III. IL-6 mRNA and serum protein 31. Folman CC, Linthorst GE, Van Mourik J, Van Willigen G, De Jonge E,
expression and the in vivo hematologic effects of IL-6. J Immunol 1991; Levi M, De Haas M, von dem Borne AE. Platelets release thrombopoietin
146: 2316-23. (TPO) upon activation: another regulatory loop in thrombocytopoiesis?
26. Stohlawetz P, Folman CC, von dem Borne AE, Pernerstorfer T, Eichler HG, Thromb Haemost 2000; 83: 923-30.
Panzer S, Jilma B. Effects of endotoxemia on thrombopoiesis in men.
Thromb Haemost 1999; 81: 613-7.
27. de la Cadena RA, Majluf-Cruz A, Stadnicki A, Tropea M, Reda D, Agosti
JM, Colman RW, Suffredini AF. Recombinant tumor necrosis factor recep- Received January 3, 2001 Accepted after resubmission September 4, 2001
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