Inflammation-induced systemic proteolysis of inter-α-inhibitor in plasma from patients with sepsis

Balduyck, Malika; Albani, Dalila; Jourdain, M.; Mizon, Charlotte; Tournoys, Antoine; Drobecq, Hervé; Fourrier, F.; Mizon, J

doi:10.1067/mlc.2000.104462

Cited by 45 publications

(31 citation statements)

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“…8, A, B, and D). A decrease of I␣I in plasma or serum has been associated with infectious disease and sepsis (32,(53)(54)(55). In lipopolysaccharide-treated mice, a model of sepsis, hepatic accumulation of HA⅐HC complexes has been observed (40), and HA⅐HC complexes have also been found in sera of patients with chronic liver disease associated with hepatitis virus infection (56).…”

Section: Discussionmentioning

confidence: 99%

Transfer of Inter-α-inhibitor Heavy Chains to Hyaluronan by Surface-linked Hyaluronan-TSG-6 Complexes

Colón

Shytuhina

Cowman

et al. 2009

Journal of Biological Chemistry

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Inter-␣-inhibitor, TSG-6, and hyaluronan have important functions in fertility and inflammation. Two subunits of inter-␣-inhibitor, the heavy chains, form covalent bonds with TSG-6 or hyaluronan in vitro. TSG-6-heavy chain complexes serve as intermediates in the transfer of heavy chains from inter-␣-inhibitor to hyaluronan. In vivo, in addition to these complexes, stable ternary complexes of hyaluronan with both TSG-6 and heavy chains have been demonstrated in the ovulatory cumulus oophorus. In our ongoing efforts to characterize the multiple interactions between hyaluronan, TSG-6 and inter-␣-inhibitor, we recently characterized the formation of highly stable complexes of TSG-6 with hyaluronan that had been tethered to a solid surface. Here we show that these hyaluronan-TSG-6 complexes are functionally active and transfer heavy chain subunits from inter-␣-inhibitor to either free or surface-bound hyaluronan. Transitional hyaluronan-TSG-6-heavy chain complexes do not accumulate in vitro. Our data show the capability for heavy chain transfer by both free TSG-6 and preformed hyaluronan-TSG-6 complexes, suggesting that both might contribute to hyaluronan modification in vivo. Transfer of heavy chains to surface-tethered hyaluronan by either free TSG-6 or surface-tethered hyaluronan-TSG-6 complexes did not affect the CD 44-mediated binding of BW 5147 cells in vitro. We show how TSG-6 and hyaluronan together can deplete inter-␣-inhibitor and generate bikunin, as has been observed in sepsis, and discuss the role of TSG-6 in the generation of hyaluronan-heavy chain complexes associated with ovulation, arthritis, and sepsis.

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Section: Discussionmentioning

confidence: 99%

Transfer of Inter-α-inhibitor Heavy Chains to Hyaluronan by Surface-linked Hyaluronan-TSG-6 Complexes

Colón

Shytuhina

Cowman

et al. 2009

Journal of Biological Chemistry

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“…Thus far, numerous studies have shown involvement of ITIs in various pathological processes, including formation of urinary tract stones (Atmani and Khan, 1999;Janssen et al, 2001), female infertility (Zhuo et al, 2001), atherosclerosis and vascular disease (Onda et al, 1999;Fujita et al, 2004), and inflammation (Balduyck et al, 2000;Yingsung et al, 2003;Pineiro et al, 2004). Furthermore, several lines of evidence suggest a potential role of ITIs in tumour biology, particularly in the metastatic cascade and tumour progression (Kobayashi et al, 1995;Bourguignon et al, 1999;Paris et al, 2002;Zhang et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

The extracellular matrix protein ITIH5 is a novel prognostic marker in invasive node-negative breast cancer and its aberrant expression is caused by promoter hypermethylation

et al. 2007

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Inter-a-trypsin inhibitors (ITIs) are protease inhibitors stabilizing the extracellular matrix. ITIs consist of one light (bikunin) and two heavy chains (ITIHs). We have recently characterized ITIH5, a novel member of the ITIH gene family, and showed that its messenger RNA is lost in a high proportion of breast tumours. In the present study, an ITIH5-specific polyclonal antibody was generated, validated with western blot and used for immunohistochemical analysis on a tissue microarray; ITIH5 was strongly expressed in epithelial cells of normal breast (n ¼ 11/15), while it was lost or strongly reduced in 42% (92/217) of invasive breast cancers. ITIH5 expression in invasive carcinomas was associated with positive expression of oestrogen receptor (P ¼ 0.008) and histological grade (P ¼ 0.024). Correlation of ITIH5 expression with clinical outcome revealed that patients with primary tumours retaining abundant ITIH5 expression had longer recurrence-free survival (RFS; P ¼ 0.037) and overall survival (OS; P ¼ 0.044), compared to those with reduced expression (mean RFS: 102 vs 78 months; mean OS: 120 vs 105 months). Methylation-specific PCR analysis frequently showed strong methylation of the ITIH5 promoter in primary breast tumours (41%, n ¼ 109) and breast cancer cell lines (n ¼ 6). Methylation was significantly associated with mRNA loss (Po0.001; n ¼ 39), and ITIH5 expression was induced after treatment of tumour cell lines with the demethylating agent 5-aza-2 0 -deoxycytidine. Moreover, ITIH5 promoter methylation was significantly associated with reduced OS (P ¼ 0.008). The cellular function of ITIH5 was evaluated by forced expression of a full-length ITIH5 complementary DNA in the breast cancer cell line MDA-MB-231, which does not endogenously express ITIH5. ITIH5-expressing clones showed a 40% reduced proliferation rate compared to mock-transfected cells. Overall, these data show that promoter methylation-mediated loss of ITIH5 expression is associated with unfavourable outcome in breast cancer patients, and thus ITIH5 could be used as a prognostic marker, although this marker is not multivariate independent due to its close association with ER expression. Our data indicate that ITIH5 is a candidate class II tumour suppressor gene and could be involved in tumour progression, invasion and metastasis, as its absence is associated with increased proliferation rates and a prognostic value indicating poor clinical outcome.

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“…Diese reicht von der Entstehung von Nierensteinen [1] und Atherosklerose [18] über weibliche Infertilität [27] und Gewebe-Inflammation [3] bis hin zur Tumorgenese, wo diese Korrelation insbesondere in Metastasierungsprozessen und der Tumorprogression gezeigt werden konnte [4,14,15,19,25]. In vorangegangenen Arbeiten haben wir ITIH5 als neues Mitglied der Gen-Familie der ITI mit schweren Ketten (ITIHs) identifiziert und gezeigt, dass die ITIH5-mRNA-Expression im humanen Mammakarzinom häufig herabreguliert wird [11,12] …”

Section: Diskussionunclassified

Novel prognostic marker in invasive breast cancer

et al. 2008

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Inflammation-induced systemic proteolysis of inter-α-inhibitor in plasma from patients with sepsis

Cited by 45 publications

References 32 publications

Transfer of Inter-α-inhibitor Heavy Chains to Hyaluronan by Surface-linked Hyaluronan-TSG-6 Complexes

Transfer of Inter-α-inhibitor Heavy Chains to Hyaluronan by Surface-linked Hyaluronan-TSG-6 Complexes

The extracellular matrix protein ITIH5 is a novel prognostic marker in invasive node-negative breast cancer and its aberrant expression is caused by promoter hypermethylation

Novel prognostic marker in invasive breast cancer

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