Bovine Lactoferrin Stimulates Human Corneal Epithelial Alkali Wound Healing In Vitro

Pattamatta, Ushasree; Willcox, Mark; Stapleton, Fiona; Cole, Nerida; Garrett, Qian

doi:10.1167/iovs.08-1882

Cited by 40 publications

(25 citation statements)

References 42 publications

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“…However, while the previous study indicated the LF-induced increase in goblet cell density, we did not observe any differences in expression of goblet cell-related genes (mucin1, mucin4, mucin5AC, and SAM pointed domain containing ets transcription factor) between the control and the LF experimental group (data not shown). Further investigation of LF-containing eye drops is necessary to confirm their presumed goblet cell increasing effect [23], [24] and the consequent improvement in the ocular surface epithelium condition [17], [25], [26].…”

Section: Discussionmentioning

confidence: 99%

Dietary Lactoferrin Alleviates Age-Related Lacrimal Gland Dysfunction in Mice

et al. 2012

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BackgroundDecrease in lacrimal gland secretory function is related to age-induced dry eye disease. Lactoferrin, the main glycoprotein component of tears, has multiple functions, including anti-inflammatory effects and the promotion of cell growth. We investigated how oral administration of lactoferrin affects age-related lacrimal dysfunction.Methods and FindingsTwelve-month-old male C57BL/6Cr Slc mice were randomly divided into a control fed group and an oral lactoferrin treatment group. Tear function was measured at a 6-month time-point. After euthanasia, the lacrimal glands were subjected to histological examination with 8-hydroxy-2′-deoxyguanosine (8-OHdG) antibodies, and serum concentrations of 8-OHdG and hexanoyl-lysine adduct (HEL) were evaluated. Additionally, monocyte chemotactic protein-1(MCP-1) and tumor necrosis factor-α (TNF-α) gene expression levels were determined by real-time PCR. The volume of tear secretion was significantly larger in the treated group than in the control. Lactoferrin administration reduced inflammatory cell infiltration and the MCP-1 and TNF-α expression levels. Serum concentrations of 8-OHdG and HEL in the lactoferrin group were lower than those in the control group and were associated with attenuated 8-OHdG immunostaining of the lacrimal glands.ConclusionOral lactoferrin administration preserves lacrimal gland function in aged mice by attenuating oxidative damage and suppressing subsequent gland inflammation.

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Section: Discussionmentioning

confidence: 99%

Dietary Lactoferrin Alleviates Age-Related Lacrimal Gland Dysfunction in Mice

et al. 2012

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“…BLf was also described to promote hyaluronan synthesis in normal human dermal fibroblasts by increasing hyaluronan synthase 2 [170], suggesting that Lf-stimulated wound healing could be related to up-regulation of hyaluronan. In corneal epithelial wound healing, bLf promotes wound closure in human corneal epithelial cells [171].…”

Section: Lactoferrin Anti-cancer Activity: Inhibition Of Cell Migratimentioning

confidence: 99%

Lactoferrin’s Anti-Cancer Properties: Safety, Selectivity, and Wide Range of Action

et al. 2020

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Despite recent advances in cancer therapy, current treatments, including radiotherapy, chemotherapy, and immunotherapy, although beneficial, present attendant side effects and long-term sequelae, usually more or less affecting quality of life of the patients. Indeed, except for most of the immunotherapeutic agents, the complete lack of selectivity between normal and cancer cells for radioand chemotherapy can make them potential antagonists of the host anti-cancer self-defense over time. Recently, the use of nutraceuticals as natural compounds corroborating anti-cancer standard therapy is emerging as a promising tool for their relative abundance, bioavailability, safety, low-cost effectiveness, and immuno-compatibility with the host. In this review, we outlined the anti-cancer properties of Lactoferrin (Lf), an iron-binding glycoprotein of the innate immune defense. Lf shows high bioavailability after oral administration, high selectivity toward cancer cells, and a wide range of molecular targets controlling tumor proliferation, survival, migration, invasion, and metastasization. Of note, Lf is able to promote or inhibit cell proliferation and migration depending on whether it acts upon normal or cancerous cells, respectively. Importantly, Lf administration is highly tolerated and does not present significant adverse effects. Moreover, Lf can prevent development or inhibit cancer growth by boosting adaptive immune response. Finally, Lf was recently found to be an ideal carrier for chemotherapeutics, even for the treatment of brain tumors due to its ability to cross the blood-brain barrier, thus globally appearing as a promising tool for cancer prevention and treatment, especially in combination therapies.

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“…18 LF promotes corneal wound healing after alkali-burn injury in mice 19 and epithelial regrowth in the in vitro studies of monolayers of corneal epithelial cells. 20,21 Using a laser-induced choroidal neovascularization murine model, we were able to demonstrated that the endogenous LF provides noticeable protection from choroidal neovascularization lesions in WT mice compared to LF knockout (LFKO) mice. Furthermore, treatment of LFKO mice with exogenous LF reduced choroidal neovascularization lesions.…”

Section: Introductionmentioning

confidence: 96%

Lactoferrin Expression in Human and Murine Ocular Tissue

Rageh¹,

Ferrington²,

Roehrich

et al. 2015

Current Eye Research

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Purpose Lactoferrin (LF) is a multifunctional protein known to provide innate defense due to its antimicrobial and anti-inflammatory properties. In the eye, LF has been identified in the tears and vitreous humor. Its presence in other ocular tissues has not been determined. Our aim is to assess the presence of LF in the cornea, iris, retina and retinal pigment epithelium (RPE) of humans and mice. Methods To test for the endogenous production of LF, reverse transcription polymerase chain reaction was performed in cultured human cells from the cornea and RPE and in murine tissues. To confirm LF localization in specific ocular tissue, immunohistochemistry was performed on flat mounts of cornea, retina and RPE in human donor eyes. The presence of LF was assessed by western blotting in human and mouse ocular tissue and human culture cells (cornea and RPE). To verify antibody specificity, purified human LF and transferrin (TF) were used on 1D and 2D western blots. Results LF gene expression was confirmed in the cornea and RPE cell cultures from humans, suggesting that LF is an endogenously produced protein. PCR results from mouse ocular tissue showed LF expression in cornea, iris, RPE, but not in retina. These results were also consistent with immunohistochemical localization of LF in human donor tissue. Antibody reaction for human LF was specific and western blotting showed its presence in the cornea, iris and RPE tissues. A faint reaction for the retina was observed but was likely due to contamination from other ocular tissues. Multiple commercially available antibodies for murine LF cross-reacted with TF, so no reliable results were obtained for murine western blot. Conclusion LF is expressed in multiple eye tissues of humans and mice. This widespread expression and multifunctional activity of LF suggests that it may play an important role in protecting eye tissues from inflammation-associated diseases.

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Bovine Lactoferrin Stimulates Human Corneal Epithelial Alkali Wound Healing In Vitro

Abstract: These results suggest that BLF at >or=2.5 mg/mL stimulates HCLE wound healing, and this stimulation is mediated through the upregulation of PDGF or IL-6.

Cited by 40 publications

References 42 publications

Dietary Lactoferrin Alleviates Age-Related Lacrimal Gland Dysfunction in Mice

Dietary Lactoferrin Alleviates Age-Related Lacrimal Gland Dysfunction in Mice

Lactoferrin’s Anti-Cancer Properties: Safety, Selectivity, and Wide Range of Action

Lactoferrin Expression in Human and Murine Ocular Tissue

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