Evidence for participation of neutrophil gelatinase‐associated lipocalin/matrix metalloproteinase‐9 (<scp>NGAL</scp>•<scp>MMP</scp>‐9) complex in the inflammatory response to infection in pregnancies complicated by preterm birth

Rood, Kara M.; Buhimschi, Irina A.; Millen, Katherine Rodewald; Bahtiyar, Mert Ozan; Thung, Stephen; Summerfield, Taryn; Zhao, Guomao; Ackerman, William E.; Shellhaas, Cynthia; Samuels, Philip; Buhimschi, Catalin S.

doi:10.1111/aji.12523

Cited by 16 publications

(11 citation statements)

References 30 publications

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“…Although lipocalin-2 has not yet been well evaluated in CVF in relation to MIAC/intraamniotic inflammation during pregnancy, lipocalin-2 is present in the vagina of healthy reproductive-age women, and its vaginal level is increased in women with vulvovaginal candidiasis [29]. A recent study on AF has shown that lipocalin-2 levels were elevated in AF with infection/inflammation [30], consistent with our results using CVF specimens.…”

Section: Discussionsupporting

confidence: 91%

Identification of Cultivable Bacteria in Amniotic Fluid Using Cervicovaginal Fluid Protein Microarray in Preterm Premature Rupture of Membranes

et al. 2020

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We aimed to identify cervicovaginal fluid (CVF) protein biomarkers of microbial invasion of the amniotic cavity (MIAC) in women with preterm premature rupture of membranes (PPROM), using an antibody microarray. This retrospective cohort study included 99 consecutive women with singleton pregnancies and PPROM (23-33 weeks) who underwent amniocentesis and who gave CVF samples. CVF proteomes from the MIAC (n = 20) versus non-MIAC groups (n = 20) were comparatively profiled by an antibody microarray using a nested case-control study design. The seven candidate biomarkers of interest were validated in the total cohort (n = 99) by enzyme-linked immunosorbent assays (ELISA). For comparison with candidate markers, amniotic fluid (AF) white blood cell (WBC) count was also measured. The primary outcome measure was MIAC (defined as positive AF culture). Thirty of the proteins studied exhibited significant intergroup differences. Measurements of the total cohort with ELISA confirmed a significant increase in the levels of CVF IL-8, lipocalin-2, MIP-1α, MMP-9, and TIMP-1 in women with MIAC, independent of gestational age at sampling. A combined, non-invasive model was developed by using a stepwise regression procedure, which included CVF IL-8 and CVF MMP-9 (area under the curve [AUC] = 0.763), and this AUC was comparable with the AUC of AF WBC. Using protein-antibody microarray technology, we found several novel, independent, non-invasive biomarkers to identify MIAC in women with PPROM: IL-8, lipocalin-2, MIP-1α, MMP-9, and TIMP-1. Furthermore, the combined non-invasive model (IL-8 and MMP-9) was a useful independent predictor for MIAC with good discriminatory power, similar to AF WBC count.

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Section: Discussionsupporting

confidence: 91%

Identification of Cultivable Bacteria in Amniotic Fluid Using Cervicovaginal Fluid Protein Microarray in Preterm Premature Rupture of Membranes

et al. 2020

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“…In particular, lipocalin-2 has been recently characterized as an adipose-derived cytokine, contributing to a low-grade inflammatory state in obese individuals 37 . In line with the known biology and function of lipocalin-2, AF levels of this protein have been reported as increased in pregnancies complicated by MIAC/histologic chorioamnioitis, IAI and preterm birth 38,39 . These results are in agreement with those of the present study.…”

Section: Discussionmentioning

confidence: 67%

Identifying potential biomarkers related to pre-term delivery by proteomic analysis of amniotic fluid

Hong

Lee

Kim

et al. 2020

Sci Rep

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We sought to identify biomarkers in the amniotic fluid (AF) and specific signaling pathways related to spontaneous preterm delivery (SPTD, < 34 weeks) in women with preterm labor (PTL) without intra-uterine infection/inflammation (IUI). This was a retrospective cohort study of a total of 139 PTL women with singleton gestation (24 + 0 to 32 + 6 weeks) who underwent amniocentesis and who displayed no evidence of IUI. A nested case–control was conducted using pooled AF samples (n = 20) analyzed via label-free liquid chromatography-tandem mass spectrometry. In the total cohort, an ELISA validation study was performed for seven candidate proteins of interest. Proteomic analysis identified 77 differentially expressed proteins (DEPs, P < 0.05) in the AF from SPTD cases compared to term delivery controls. ELISA validation confirmed that women who had an SPTD before 34 weeks had significantly independently lower levels of VEGFR-1 and higher levels of lipocalin-2 and the Fc fragment of IgG binding protein in the AF. Five principle pathways associated with the 77 DEPs were identified, including glycolysis, gluconeogenesis, and iron homeostasis. The proteomic analysis data of AFs from women with PTL identified several novel biomarkers and specific protein pathways related to SPTD in the absence of IUI.

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“…For instance, MMP9 plays an important role in neutrophil migration across the endothelial barrier into tissues, which has implications in bullous pemphigoid or other skin diseases (39,63,64). Also, MMP9 can be secreted to form a complex with LCN2, and this MMP9-neutrophil gelatinase-associated lipocalin complex has been associated with cancer metastasis and inflammation (65,66). Furthermore, S100A9 protein in exosomes from chronic lymphocytic leukemia cells promotes NF-kB activity and disease progression (67), and exosomes showing common and unique proteins.…”

Section: Discussionmentioning

confidence: 99%

Neutrophil exosomes enhance the skin autoinflammation in generalized pustular psoriasis via activating keratinocytes

et al. 2019

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Generalized pustular psoriasis (GPP) is a rare and severe inflammatory skin disease that can be life‐threatening. Gene mutations are found in some cases, but its immune pathogenesis is largely unknown. Here, we observed that the neutrophil:lymphocyte ratio in patients with GPP was higher than that in healthy controls and decreased after effective treatment. Neutrophils isolated from patients with GPP induced higher expressions of inflammatory genes including IL‐1β, IL‐36G, IL‐18, TNF‐α, and C‐X‐C motif chemokine ligands in keratinocytes than normal neutrophils did. Moreover, neutrophils from patients with GPP secreted more exosomes than controls, which were then rapidly internalized by keratinocytes, increasing the expression of these inflammatory molecules via activating NF‐κB and MAPK signaling pathways. The proteomic profiles in neutrophil exosomes further characterized functional proteins and identified olfactomedin 4 as the critical differentially expressed protein that mediates the autoimmune inflammatory responses of GPP. These results demonstrate that neutrophil exosomes have an immune‐regulatory effect on keratinocytes, which modulates immune cell migration and autoinflammation in GPP.—Shao, S., Fang, H., Zhang, J., Jiang, M., Xue, K., Ma, J., Zhang, J., Lei, J., Zhang, Y., Li, B., Yuan, X., Dang, E., Wang, G. Neutrophil exosomes enhance the skin autoinflammation in generalized pustular psoriasis via activating keratinocytes. FASEB J. 33, 6813–6828 (2019). http://www.fasebj.org

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Evidence for participation of neutrophil gelatinase‐associated lipocalin/matrix metalloproteinase‐9 (NGAL•MMP‐9) complex in the inflammatory response to infection in pregnancies complicated by preterm birth

Cited by 16 publications

References 30 publications

Identification of Cultivable Bacteria in Amniotic Fluid Using Cervicovaginal Fluid Protein Microarray in Preterm Premature Rupture of Membranes

Identification of Cultivable Bacteria in Amniotic Fluid Using Cervicovaginal Fluid Protein Microarray in Preterm Premature Rupture of Membranes

Identifying potential biomarkers related to pre-term delivery by proteomic analysis of amniotic fluid

Neutrophil exosomes enhance the skin autoinflammation in generalized pustular psoriasis via activating keratinocytes

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