Lactoferrin or a Fragment Thereof Inhibits the Endotoxin-Induced Interleukin-6 Response in Human Monocytic Cells

Mattsby‐Baltzer, Inger; Roșeanu, Anca; Motas, Cecilia; Elverfors, Johan; Engberg, I; Hanson, Lars Å.

doi:10.1203/00006450-199608000-00011

Cited by 171 publications

(140 citation statements)

References 43 publications

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“…Some maternal milk constituents have been reported to have anti-inflammatory activity. Lactoferrin and fragments of lactoferrin have been shown to inhibit the endotoxininduced interleukin 6 release from human monocytic cells (Mattsby-Baltzer et al 1996). The cytokines interleukin 10 and TGFβ have been documented in maternal milk, and are also recognized to have immuno-suppressive and antiinflammatory activity (Letterio et al 1994;Garofalo et al 1995).…”

Section: Maternal Milk and Anti-inflammatory Functionmentioning

confidence: 99%

Early nutrition and the development of immune function in the neonate

Kelly¹,

Coutts²

2000

Proc. Nutr. Soc.

175

119

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The present review will concentrate on the development of the gut-associated lymphoid tissue and the role of early nutrition in promoting immune function. The intestine is the largest immune organ in the body, and as such is the location for the majority of lymphocytes and other immune effector cells. The intestine is exposed to vast quantities of dietary and microbial antigens, and is the most common portal of entry for pathogens, some of which are potentially lethal. The development of normal immune function of the intestine is therefore vital for survival, and is dependent on appropriate antigen exposure and processing, and also an intact intestinal barrier. In early life innate mechanisms of defence are probably more important than active or adaptive mechanisms in responding to an infectious challenge, since the healthy neonate is immunologically naïve (has not seen antigen) and has not acquired immunological memory. During this period maternal colostrum and milk can significantly augment resistance to enteric infections. The mechanisms of enhancing disease resistance are thought to be passive, involving a direct supply of anti-microbial factors, and active, by promoting the development of specific immune function. A tolerance response to dietary and non-invasive antigens is generally induced in the gut. However, it must also be able to mount an adequate immune response to ensure clearance of foreign antigens. It is now recognized that regulation of tolerance and active immune responses is critical to health, and failure to regulate these responses can lead to recurrent infections, inflammatory diseases and allergies. The education of the immune system in early life is thought to be critical in minimizing the occurrence of these immune-based disorders. During this phase of development maternal milk provides signals to the immune system that generate appropriate response and memory. One factor that has been proposed to contribute to the increase in the incidence of immune-based disorders, e.g. atopic diseases in Western countries, is thought to be the increased prevalence of formula-feeding.

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Section: Maternal Milk and Anti-inflammatory Functionmentioning

confidence: 99%

Early nutrition and the development of immune function in the neonate

Kelly¹,

Coutts²

2000

Proc. Nutr. Soc.

175

119

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“…Human Lf was found to bind to the lipid A of bacterial lipopolysaccharides (LPS) with high affinity, resulting in the neutralization of LPS by preventing LPS from interacting with the main actors of LPS signaling, like LPS-binding protein (LBP), soluble CD14 (sCD14) and membrane CD14 (mCD14) [93]. Bovine Lf also is able to reduce the endotoxin-induced response of inflammatory cells [102], but the contribution of Lf to the control of inflammation during E. coli mastitis remains to be demonstrated.…”

Section: Humoral Defensesmentioning

confidence: 99%

Innate immunity of the bovine mammary gland

2006

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-Understanding the immune defenses of the mammary gland is instrumental in devising and developing measures to control mastitis, the major illness of dairy ruminants. Innate immunity is an extremely broad field for investigation, and despite decades of research, our present knowledge of the innate defenses of the udder is incomplete. Yet, information is being gained on the recognition of pathogens by the mammary gland, and on several locally inducible defenses. The contribution of mammary epithelial cells to local defenses and to the mobilization of leucocytes is under growing scrutiny. Interactions of mastitis-causing bacteria such as Escherichia coli or Staphylococcus aureus and the mammary gland represents a suitable model for studies on innate immunity at an epithelium frontier. Powerful new research tools are radically modifying the prospects for the understanding of the interplay between the mammary gland innate defenses and mastitis-causing bacteria: genetic dissection of the immune response, microarray gene technology, transcriptomic methodologies and gene silencing by RNA interference will make possible the discovery of several of the key defense mechanisms which govern the susceptibility/resistance to mastitis at the molecular and genetic levels. It should then be possible to enhance the resistance of dairy ruminants to mastitis through immunomodulation and genetic improvement. mastitis / cattle / innate immunity / inflammation / milk

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“…[6][7][8][9] In addition to its ability to kill bacteria, lactoferrin can also neutralize endotoxin and inhibit the induction of NFkB in monocytes in response to LPS, resulting in lowered IL-6 and TNF-alpha production. [10][11][12] Lactoferrin is present in high concentrations in saliva and is thought to play a particularly important role in regulation of those bacteria present within the oral cavity. This protein regulates several bacteria that are associated with periodontal disease, including Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi), Prevotella melaninogenica (Pm) and Actinobacillus actinomycetemcomitans (Aa).…”

mentioning

confidence: 99%

A nonconservative, coding single-nucleotide polymorphism in the N-terminal region of lactoferrin is associated with aggressive periodontitis in an African-American, but not a Caucasian population

et al. 2005

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Lactoferrin is an antimicrobial protein which plays an important role in regulating bacteria that are associated with aggressive periodontitis. Lactoferrin kills directly (via its strongly cationic N-terminal region) and indirectly, through sequestering the iron that bacteria require for growth. As aggressive periodontitis has a strong heritable component, we hypothesized that genetic variation within the lactoferrin gene may play a role in susceptibility to this condition. We have identified and examined a novel, functional, single-point A/G nucleotide mutation causing a threonine/alanine substitution at position 11 (T11A) of the secreted lactoferrin protein. In a pilot case-controlled study of aggressive periodontitis, analysis of 46 African-American patients and 78 controls showed that patients were twice as likely to express the G nucleotide (alanine) allele over controls (60.3 vs 30.4%; P ¼ 0.0007, odds ratio ¼ 2.564, 95% CI ¼ 1. 475-4.459). A Caucasian population of 77 patients and 131 controls showed no such association (P ¼ 0.5201, odds ratio ¼ 0.862, 95% CI ¼ 0.548-1.356). The data presented provide a new insight into the genetic susceptibility to aggressive periodontitis. Genes and Immunity (2005) Lactoferrin is an 80 kDa cationic protein with strong antibacterial and immunomodulatory functions. [1][2][3][4][5] The antibacterial properties were originally attributed solely to its ability to bind the iron necessary for bacterial growth. However, it has been established more recently that lactoferrin also binds to bacteria and kills through direct interactions governed by its strongly basic Nterminal region. [6][7][8][9] In addition to its ability to kill bacteria, lactoferrin can also neutralize endotoxin and inhibit the induction of NFkB in monocytes in response to LPS, resulting in lowered IL-6 and TNF-alpha production. [10][11][12] Lactoferrin is present in high concentrations in saliva and is thought to play a particularly important role in regulation of those bacteria present within the oral cavity. This protein regulates several bacteria that are associated with periodontal disease, including Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi), Prevotella melaninogenica (Pm) and Actinobacillus actinomycetemcomitans (Aa). [13][14][15][16][17][18] Lactoferrin's effects on Aa, which is considered to have the strongest association with aggressive periodontitis, occurs through direct killing, as well as through inhibition of attachment to epithelial cells and the development of biofilms. 14,19,20 Studies examining the pattern of inheritance of aggressive periodontitis in families suggest a genetic basis for susceptibility. 18,21 The disease is particularly common within African-American populations, being up to 15 times more prevalent than in Caucasians. 21 As lactoferrin has been shown to be active against a number of pathogenic bacteria, including Aa, we hypothesized that single-nucleotide polymorphism (SNPs) within the lactoferrin gene could play a role in the genetic susceptibility that is s...

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Lactoferrin or a Fragment Thereof Inhibits the Endotoxin-Induced Interleukin-6 Response in Human Monocytic Cells

Cited by 171 publications

References 43 publications

Early nutrition and the development of immune function in the neonate

Early nutrition and the development of immune function in the neonate

Innate immunity of the bovine mammary gland

A nonconservative, coding single-nucleotide polymorphism in the N-terminal region of lactoferrin is associated with aggressive periodontitis in an African-American, but not a Caucasian population

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