Lactoferrin moderates LPS-induced hypotensive response and gut injury in rats

Doursout, Marie–Françoise; Horton, Haley; Hoang, Linh; Liang, Yangyan; Hwang, Shen-An; Boyd, Sydney; Actor, Jeffrey K.; Kruzel, Marian L.

doi:10.1016/j.intimp.2012.12.009

Cited by 23 publications

(20 citation statements)

References 36 publications

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“…Obesity, IR and T2D are characterized by an inflammatory state [33, 34]. In this context, metabolic endotoxemia [higher plasma LPS levels] as a consequence of raised gut permeability has been proposed as the main cause for the inflammatory state [33, 34].…”

Section: Discussionmentioning

confidence: 99%

“…In this context, metabolic endotoxemia [higher plasma LPS levels] as a consequence of raised gut permeability has been proposed as the main cause for the inflammatory state [33, 34]. To approach the mechanisms of action, we assessed Lf expression in the intestine and impact of IR and bacterial LPS.…”

Section: Discussionmentioning

confidence: 99%

“…This highly suggests that the intestine may be an important and finely regulated contributor of circulating Lf. Interestingly, normal gut functions and intestinal barrier permeability were restored by exogenous Lf administration in LPS-challenged rats [33, 34] through various mechanisms (i), modulation of immune functions [35–37]; (ii) regulation of intestinal microbiota [35–37]; (iii) abolition of LPS-induced reactive oxygen species production [38]; (iv) inhibition of LPS binding to its receptors (i.e. CD14) [39]; and (v) reduction of OxS through L-selectin competition [40].…”

Section: Discussionmentioning

confidence: 99%

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Plasma Lactoferrin Levels Positively Correlate with Insulin Resistance despite an Inverse Association with Total Adiposity in Lean and Severely Obese Patients

et al. 2016

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ContextLactoferrin (Lf) is an important protein found on mucosal surfaces, within neutrophils and various cells, and in biological fluids. It displays multiple functions, including iron-binding as well as antimicrobial, immunomodulatory and anti-inflammatory activities. Although Lf ingestion has been suggested to cause adiposity reduction in murine models and humans, its relationship with insulin resistance (IR) has not been studied thoroughly.ObjectiveTo establish the association between circulating Lf levels, glucose status and blood lipid/lipoprotein profile.MethodsTwo independent cohorts were examined: lean to moderately obese women admitted for gynecological surgery (n = 53) and severely obese subjects undergoing biliopancreatic diversion (n = 62).ResultsAlthough body mass index (BMI) and total body fat mass were negatively associated with Lf, IR (assessed by the HOMA-IR index) was positively and independently associated with plasma Lf concentrations of the first cohort of lean to moderately obese women. These observations were validated in the second cohort in view of the positive correlation between plasma Lf concentrations and the HOMA-IR index, but without a significant association with the body mass index (BMI) of severely obese subjects. In subsamples of severely obese subjects matched for sex, age and BMI, but with either relatively low (1.89 ± 0.73) or high (13.77 ± 8.81) IR states (according to HOMA-IR), higher plasma Lf levels were noted in insulin-resistant vs insulin-sensitive subjects (P<0.05). Finally, Lf levels were significantly higher in lean to moderately obese women than in severely obese subjects (P<0.05).ConclusionOur findings revealed that plasma Lf levels are strongly associated with IR independently of total adiposity, which suggests an intriguing Lf regulation mechanism in conditions of obesity and IR.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Plasma Lactoferrin Levels Positively Correlate with Insulin Resistance despite an Inverse Association with Total Adiposity in Lean and Severely Obese Patients

et al. 2016

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“…244 Although the exact contribution of Intelectin-1 to barrier properties of the gut remains to be resolved, its role in the uptake of LF may be critical given the anti-inflammatory effects of LF and its capacity to reduce both bacterial infection, and the effects of LPS, in murine models. 245,246 …”

Section: Membrane Transportmentioning

confidence: 99%

IBD Candidate Genes and Intestinal Barrier Regulation

McCole

2014

Inflammatory Bowel Diseases

127

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Technological advances in the large scale analysis of human genetics have generated profound insights into possible genetic contributions to chronic diseases including the inflammatory bowel diseases (IBDs), Crohn’s disease and ulcerative colitis. To date, 163 distinct genetic risk loci have been associated with either Crohn’s disease or ulcerative colitis, with a substantial degree of genetic overlap between these 2 conditions. Although many risk variants show a reproducible correlation with disease, individual gene associations only affect a subset of patients, and the functional contribution(s) of these risk variants to the onset of IBD is largely undetermined. Although studies in twins have demonstrated that the development of IBD is not mediated solely by genetic risk, it is nevertheless important to elucidate the functional consequences of risk variants for gene function in relevant cell types known to regulate key physiological processes that are compromised in IBD. This article will discuss IBD candidate genes that are known to be, or are suspected of being, involved in regulating the intestinal epithelial barrier and several of the physiological processes presided over by this dynamic and versatile layer of cells. This will include assembly and regulation of tight junctions, cell adhesion and polarity, mucus and glycoprotein regulation, bacterial sensing, membrane transport, epithelial differentiation, and restitution.

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“…In a highly activated inflammatory environment, such as under lipopolysaccharide (LPS) stimulation, the addition of lactoferrin actively decreased macrophage production of inflammatory cytokines TNF-α and IL-12 (Hwang et al 2007a; Doursout et al 2013). During low antigen stimulation, such as vaccination with the TB vaccine BCG (Bacillus Calmette Guerin), the addition of lactoferrin enhanced vaccine efficacy by increasing the antigen recall IFN-γ response (Hwang et al 2005, 2007b, 2009a, 2009b, 2011a, 2011b; Hwang and Actor 2009), which is necessary for the control of MTB infection.…”

Section: Introductionmentioning

confidence: 99%

Oral recombinant human or mouse lactoferrin reducesMycobacterium tuberculosisTDM induced granulomatous lung pathology

Hwang

Kruzel

Actor

2017

Biochem. Cell Biol.

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Trehalose 6'6-dimycolate (TDM) is the most abundant glycolipid on the cell wall of Mycobacterium tuberculosis (MTB). TDM is capable of inducing granulomatous pathology in mouse models that resembles those induced by MTB infection. Using the acute TDM model, this work investigates the effect of recombinant human and mouse lactoferrin to reduce granulomatous pathology. C57BL/6 mice were injected intravenously with TDM at a dose of 25 μg-mouse-1. At day 4 and 6, recombinant human or mouse lactoferrin (1 mg · (100 μL)−1 mouse−1) were delivered by gavage. At day 7 after TDM injection, mice were evaluated for lung pathology, cytokine production, and leukocyte populations. Mice given human or mouse lactoferrin had reduced production of IL-12p40 in their lungs. Mouse lactoferrin increased IL-6 and KC (CXCL1) in lung tissue. Increased numbers of macrophages were observed in TDM-injected mice given human or mouse lactoferrin. Granulomatous pathology, composed of mainly migrated leukocytes, was visually reduced in mice that received human or mouse lactoferrin. Quantitation of granulomatous pathology demonstrated a significant decrease in mice given human or mouse lactoferrin compared with TDM control mice. This report is the first to directly compare the immune modulatory effects of both heterologous recombinant human and homologous mouse lactoferrin on the development of TDM-induced granulomas.

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Lactoferrin moderates LPS-induced hypotensive response and gut injury in rats

Cited by 23 publications

References 36 publications

Plasma Lactoferrin Levels Positively Correlate with Insulin Resistance despite an Inverse Association with Total Adiposity in Lean and Severely Obese Patients

Plasma Lactoferrin Levels Positively Correlate with Insulin Resistance despite an Inverse Association with Total Adiposity in Lean and Severely Obese Patients

IBD Candidate Genes and Intestinal Barrier Regulation

Oral recombinant human or mouse lactoferrin reducesMycobacterium tuberculosisTDM induced granulomatous lung pathology

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