Bovine lactoferrin induces interleukin-11 production in a hepatitis mouse model and human intestinal myofibroblasts

Kuhara, Tetsuya; Yamauchi, Koji; Iwatsuki, Keiji

doi:10.1007/s00394-011-0219-y

Cited by 11 publications

(14 citation statements)

References 33 publications

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“…The decrease of Bcl-2 is considered as an important event to the opening of the MPT pore and loss of the mitochondrial membrane potential, for the release of cytochrome c and other pro-apoptotic proteins characteristic of the intrinsic apoptosis pathway (Lin et al, 2005). It is known that the tumour suppressor gene p53 has a critical role in the regulation of Bcl-2 and other proteins of the Bcl-2 family (Kuhara et al, 2012). As we previously discussed, the p53 has probably a key role in the apoptosis selectively induced in MCF-7 cells as compared with the other used breast cancer cells.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, the potential of LF for application in cancer therapy was further confirmed in vivo. In those experiments, the anticancer effect of LF was shown to be mainly exerted through activation of both the innate and adaptive immune responses, as well as through the stimulation of the proliferation and differentiation of T helper cells (Th) into type 1 helper cell (Th1) or type 2 helper cell (Th2) phenotypes, which release tumour-killing cytokines (tumour necrosis factors (TNF), interferon-g (IFN-g), caspase-1 and interleukin-18 (IL-18)) in the intestine and tumour (De la Rosa, Yang, Tewary, Varadhachary, & Oppenheim, 2008;Fischer, Debbabi, Dubarry, Boyaka, & Tome, 2006;Kuhara, Yamauchi, & Iwatsuki, 2012).…”

Section: Introductionmentioning

confidence: 99%

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In vitro evaluation of bovine lactoferrin potential as an anticancer agent

Zhang¹,

Lima²,

Rodrigues³

2015

International Dairy Journal

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Bovine lactoferrin (bLF) was shown to efficiently inhibit the growth of MCF-7, T-47D, MDA-MB-231 and Hs578T breast cancer cells in a concentration-dependent manner. However, apoptosis was only induced in MCF-7 cells, which was associated with the mitochondria membrane depolarisation and a decrease of Bcl-2 levels. bLF led to the cycle arrest of MCF-7 cells at G1/G0 phase, as well as a significant decrease in the expression of CDC25c. The possibility that the observed anticancer effects could be due to the high exogenous bLF concentrations in the culture media was excluded. Moreover, bLF was shown to restrain the colony formation of MCF-7 cells, although it promoted cell migration. This later effect was unspecific and related to the presence of a high protein concentration in the culture or medium. The results gathered in this work provide valuable insights for the evaluation and further study of the potential of bLF in cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

In vitro evaluation of bovine lactoferrin potential as an anticancer agent

Zhang¹,

Lima²,

Rodrigues³

2015

International Dairy Journal

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“…In a mice model of hepatitis induced by intraperitoneal co-administration of LPS and zymosan, orally administered bLf decreased the serum aspartate aminotransferase activity (a marker of liver inflammation), and increased in the small intestine the production of IL-11, an anti-inflammatory cytokine with a role in the amelioration of inflammatory response [153,164]. The findings indicate that the up-modulation of IL-11 levels by bLf seems to provide therapeutic action in the small intestine induced by LPS-zymosan in this model of hepatitis.…”

Section: Lactoferrin As Anti-inflammatory In Infectious Diseasesmentioning

confidence: 99%

Lactoferrin: Balancing Ups and Downs of Inflammation Due to Microbial Infections

Drago-Serrano

Campos-Rodrı́guez

Carrero

et al. 2017

IJMS

109

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Lactoferrin (Lf) is a glycoprotein of the primary innate immune-defense system of mammals present in milk and other mucosal secretions. This protein of the transferrin family has broad antimicrobial properties by depriving pathogens from iron, or disrupting their plasma membranes through its highly cationic charge. Noteworthy, Lf also exhibits immunomodulatory activities performing up- and down-regulation of innate and adaptive immune cells, contributing to the homeostasis in mucosal surfaces exposed to myriad of microbial agents, such as the gastrointestinal and respiratory tracts. Although the inflammatory process is essential for the control of invasive infectious agents, the development of an exacerbated or chronic inflammation results in tissue damage with life-threatening consequences. In this review, we highlight recent findings in in vitro and in vivo models of the gut, lung, oral cavity, mammary gland, and liver infections that provide experimental evidence supporting the therapeutic role of human and bovine Lf in promoting some parameters of inflammation and protecting against the deleterious effects of bacterial, viral, fungal and protozoan-associated inflammation. Thus, this new knowledge of Lf immunomodulation paves the way to more effective design of treatments that include native or synthetic Lf derivatives, which may be useful to reduce immune-mediated tissue damage in infectious diseases.

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“…cultured intestinal epithelial cells, myofibroblasts or monocytes (20) . In the present study, bLF-induced enhancement of BMP2 production was reduced in IL-11Ra-null mice (Fig.…”

Section: Discussionmentioning

confidence: 99%

Bovine lactoferrin ingestion protects against inflammation via IL-11 induction in the small intestine of mice with hepatitis

et al. 2014

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Accumulating evidence suggests that orally ingested lactoferrin protects against inflammation. To assess the efficacy of orally administered bovine lactoferrin (bLF) against hepatitis and to identify the underlying mechanism, in the present study, we used four mouse models of hepatitis induced by D-galactosamine (GalN), carbon tetrachloride (CCl 4 ), GalN plus lipopolysaccharide (LPS) and zymosan plus LPS. Intraperitoneal (i.p.) injection of GalN (500 mg/kg body weight) in mice treated with bovine serum albumin (BSA) for 14 d significantly increased serum aspartate aminotransferase (AST) concentrations compared with the untreated mice. However, orally administered bLF reduced AST concentrations compared with BSA treatment. In mice that received a single injection (0·4 ml/kg) and twice-weekly injections (0·08 ml/kg) of CCl 4 for 24 weeks and pretreated with bLF for 14 d and 24 weeks, respectively, significantly suppressed alanine aminotransferase and AST concentrations were observed compared with the BSA-treated control. Oral administration of bLF for 14 d before i.p. injection of LPS (5 mg/kg) plus GalN (1 g/kg) significantly improved the survival rate. In mice that received intravenous injection of zymosan (25 mg/kg) and LPS (15 mg/kg) at 7 d intervals, bLF reduced the elevation of AST concentrations and enhanced the production of IL-11 and bone morphogenetic protein 2 in the small intestine compared with the BSA-treated control. To evaluate the effects of IL-11, we used IL-11 receptor a-null mice treated with GalN, CCl 4 and zymosan plus LPS. In this group, the activity of bLF was not significantly different from that of BSA. These data indicate that orally ingested bLF enhances the expression of IL-11 in the small intestine and up-regulates protective activity in mice with hepatitis.

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Bovine lactoferrin induces interleukin-11 production in a hepatitis mouse model and human intestinal myofibroblasts

Abstract: bLF upregulated the activity of anti-inflammatory factors, such as IL-11, in the intestine of a hepatitis mouse model and human intestinal myofibroblasts.

Cited by 11 publications

References 33 publications

In vitro evaluation of bovine lactoferrin potential as an anticancer agent

In vitro evaluation of bovine lactoferrin potential as an anticancer agent

Lactoferrin: Balancing Ups and Downs of Inflammation Due to Microbial Infections

Bovine lactoferrin ingestion protects against inflammation via IL-11 induction in the small intestine of mice with hepatitis

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