Antileukoprotease; An endogenous protein in the innate mucosal defense against fungi

Tomee, J. F. C.; Hiemstra, Pieter S.; Heinzel‐Wieland, Regina; Kauffman, Henk F.

doi:10.1016/s0165-2478(97)85719-7

Cited by 42 publications

(56 citation statements)

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“…This two-domain polypeptide has a carboxy-terminal domain expressing antiproteinase activity, whereas its aminoterminal domain has broadspectrum antimicrobial properties (Tomee et al, 1997). LPS and lipoteichoic acid from Gram-positive bacteria cell walls have also been shown to induce SLPI synthesis in murine macrophages (Jin et al, 1998).…”

Section: Granule Proteinsmentioning

confidence: 99%

Neutrophils: Molecules, Functions and Pathophysiological Aspects

Witko‐Sarsat

Rieu

Descamps‐Latscha

et al. 2000

Laboratory Investigation

951

723

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Section: Granule Proteinsmentioning

confidence: 99%

Neutrophils: Molecules, Functions and Pathophysiological Aspects

Witko‐Sarsat

Rieu

Descamps‐Latscha

et al. 2000

Laboratory Investigation

951

723

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“…[11][12][13] These antimicrobial polypeptides, some of which are induced in response to PAMP exposure, are effective at inhibiting Gram-positive and Gram-negative bacteria, fungi, and enveloped viruses, including Neisseria gonorrhoeae, Chlamydia trachomatis, Candida albicans, Herpes Simplex Virus-2, and Human Immunodeficiency Virus-1. [14][15][16][17][18][19][20][21][22][23] It is well known that estrogens, which act throughout the body, have both anti-inflammatory and proinflammatory functions. For example, E 2 enhances the production of proinflammatory interferon-γ and anti-inflammatory IL-10 in T cells.…”

Section: Introductionmentioning

confidence: 99%

Estradiol selectively regulates innate immune function by polarized human uterine epithelial cells in culture

et al. 2008

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The goal of this study was to examine the role of E 2 in regulating innate immune protection by human uterine epithelial cells (UECs). Recognizing that UECs produce cytokines and chemokines to recruit and activate immune cells as well as viral and bacterial antimicrobials, we sought to examine the effect of E 2 on constitutive and Toll-like receptor (TLR) agonist (lipopolysaccharide (LPS) and poly (I:C))-induced immune responses. The secretion by polarized UECs in culture of interleukin (IL)-6, macrophage inhibitory factor (MIF), and secretory leukocyte protease inhibitor (SLPI) was examined as well as the mRNA expression of human β-defensin-2 (HBD2), tumor necrosis factor (TNF)-α, IL-8, and nuclear factor (NF)-kB. When incubated with E 2 for 24-48 h, we found that E 2 stimulated UEC secretion of SLPI (fourfold) and mRNA expression of HBD2 (fivefold). Moreover, when antibacterial activity in UEC secretions was measured using Staphylococcus aureus, E 2 increased the secretion of soluble factor(s) with antibacterial activity. In contrast, E 2 had no effect on constitutive secretion of proinflammatory cytokines and chemokines by UECs but completely inhibited LPS-and poly (I:C)-induced secretion of MIF, IL-6, and IL-8. Estradiol also reversed the stimulatory effects of IL-1β on mRNA expression of TNF-α, IL-8, and NF-kB by 85, 95, and 70%, respectively. As SLPI is known to inhibit NF-kB expression, these findings suggest that E 2 inhibition of proinflammatory cytokines may be mediated through SLPI regulation of NF-kB. Overall, these findings indicate that the production of cytokines, chemokines, and antimicrobials by UECs are differentially regulated by E 2 . Further, it suggests that with E 2 regulation, epithelial cells that line the uterine cavity have evolved immunologically to be sensitive to viral and bacterial infections as well as the constraints of procreation.

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“…The protease inhibitory sequence has been identified in the carboxy domain (Meckelein et al 1991). Although initially described as a potent inhibitor of neutrophil elastase and cathepsin-G (Thompson & Ohlsson 1986), secretory leukocyte protease inhibitor has many other functions, including inhibition of mast cell kinases (Pemberton et al 1998), as an anti-bacterial (Hiemstra et al 1996), anti-viral (Shine et al 1997) and anti-fungal (Tomee et al 1997) agent and anti-coagulant (Masuda et al 1995). In addition, it has recently been shown to inhibit the release of matrix metalloproteinases by monocytes via inhibition of cyclo-oxygenase-2 (Zhang et al 1997) and the lipopolysaccharide-induced activation of the proinflammatory transcription factor, NF B ( Jin et al 1997).…”

Section: Introductionmentioning

confidence: 99%

Secretory leukocyte protease inhibitor concentration increases in amniotic fluid with the onset of labour in women: characterization of sites of release within the uterus

Denison¹,

Kelly²,

Calder³

et al. 1999

Journal of Endocrinology

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Secretory leukocyte protease inhibitor is a potent inhibitor of neutrophil function, a mediator of mucosal immunity and an inhibitor of NF B regulated inflammatory responses. However, its source, function and regulation within the uterus during pregnancy and at parturition are not well defined. In amniotic fluid, the concentration of secretory leukocyte protease inhibitor increased significantly from 2nd trimester (24 3 ng/ml; mean ...; n=20) to term (751 53 ng/ml; P<0·05; n=15) with a further profound increase (P<0·005) with the onset of labour (3929 1076 ng/ml; n=15). To establish the intrauterine sites of secretion, explants (n=6 different patients per tissue) were collected at term after elective caesarean section. High levels of secretory leukocyte protease inhibitor were released by decidua (135·2 12·4 pg/mg; mean ...) and chorio-decidua (325·1 26·4 pg/mg) with less by amnion (55·6 6·0 pg/mg) and placenta (9·2 1·9 pg/mg). Intense immunoreactivity for secretory leukocyte protease inhibitor was detected predominantly in decidua parietalis cells adherent to the chorion laeve and myometrium, and also in decidua basalis. We propose that, within the pregnant uterus, secretory leukocyte protease inhibitor is released by decidua, fetal membranes and potentially the fetal lung. The increase in secretory leukocyte protease inhibitor may act to modulate proinflammatory paracrine interactions for the maintenance of pregnancy and limit those occurring at parturition within the uterus.

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Antileukoprotease; An endogenous protein in the innate mucosal defense against fungi

Cited by 42 publications

References 0 publications

Neutrophils: Molecules, Functions and Pathophysiological Aspects

Neutrophils: Molecules, Functions and Pathophysiological Aspects

Estradiol selectively regulates innate immune function by polarized human uterine epithelial cells in culture

Secretory leukocyte protease inhibitor concentration increases in amniotic fluid with the onset of labour in women: characterization of sites of release within the uterus

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